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UNTANGLING THE WEB OF

ANTIRETROVIRAL PRICE REDUCTIONS

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1. Equal stature of both logos

13th Edition July 2010

Médecins Sans Frontières | July 2010

THE MSF CAMPAIGN FOR ACCESS TO ESSENTIAL MEDICINES

Eleven years ago, on the heels of Médecins Sans Frontières (MSF) being awarded the Nobel Peace Prize – and largely in response to the inequalities surrounding access to AIDS treatment between rich and poor countries – MSF launched the Campaign for Access to Essential Medicines. Its sole purpose has been to push for access to, and the development of life-saving and life-prolonging medicines, diagnostics and vaccines for patients in MSF programmes and beyond.

UNTANGLING THE WEB ONLINE!Médecins Sans Frontières’ guide to the prices of AIDS medicines is now in its 13th edition – and is also available in an online version. Stay up-to-date with the latest news on ARV prices and availability by checking:

utw.msfaccess.org

Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org �

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TABLE OF CONTENTS

BACkGROUND: ACCESS TO ANTIRETROVIRALS 3 AIDSProgressUnderSiege:TheEmergencyIsFarfromOver

4 Challenges:Second-ClassAIDSTreatment

9 OvercomingChallenges:StavingofftheSecondWaveoftheAccessCrisis

14 AIDSTreatmentDelayed,Deferred,Denied

15 Conclusion

16 QualityIssues

17 Methodology

18 HowtoReadtheDrugProfiles

DRUG PROFILES

ENTRy INHIBITORS

19 Maraviroc(MVC)

FUSION INHIBITORS

20 Enfuvirtide

INTEGRASE INHIBITORS

21 Raltegravir(RAL)

NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI)

22 Efavirenz(EFV)

24 Etravirine(ETV)

25 Nevirapine(NVP)

NUCLEOSIDE & NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI & NtRTI)

27 Abacavir(ABC)

29 Didanosine(ddI)

31 Emtricitabine(FTC)

32 Lamivudine(3TC)

34 Stavudine(d4T)

36 Tenofovirdisoproxilfumarate(TDF)

38 Zidovudine(AZTorZDV)

PROTEASE INHIBITORS (PI)

40 (ATV)

42 Darunavir(DRV)

44 Fosamprenavir(FPVorf-APV)

45 Indinavir(IDV)

46 Lopinavir/ritonavir(LPV/r)

48 Nelfinavir(NFV)

50 Ritonavir(rorRTV)

52 Saquinavir(SQV)

54 Tipranavir(TPV) Continued overleaf

Médecins Sans Frontières | July 2010�

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FIxED-DOSE COMBINATIONS AND CO-PACkS

55 Abacavir/lamivudine(ABC/3TC)

57 Lamivudine/stavudine(3TC/d4T)

59 Lamivudine/stavudine/nevirapine(3TC/d4T/NVP)

61 Lamivudine/stavudine+efavirenz(3TC/d4T+EFV)

62 Tenofovirdisoproxilfumarate/emtricitabine(TDF/FTC)

64 Tenofovirdisoproxilfumarate/emtricitabine/efavirenz(TDF/FTC/EFV)

66 Tenofovirdisoproxilfumarate/lamivudine(TDF/3TC)

68 Tenofovirdisoproxilfumarate/lamivudine/efavirenz(TDF/3TC/EFV)

70 Zidovudine/lamivudine(AZT/3TC)

72 Zidovudine/lamivudine/abacavir(AZT/3TC/ABC)

74 Zidovudine/lamivudine/nevirapine(AZT/3TC/NVP)

76 Zidovudine/lamivudine+efavirenz(AZT/3TC+EFV)

ANNExES 77 Annex1:SummaryofTable–AllPricesonOnePage

81 Annex2:ConditionsofOfferbyCompany

84 Annex3:Least-DevelopedCountries(LDCs)

84 Annex4:HumanDevelopmentIndex(HDI)

84 Annex5:Sub-SaharanCountries

84 Annex6:WorldBankClassificationofEconomies

85 Annex7:Bristol-MyersSquibbEligibleCountries

85 Annex8:AbbottEligibleCountries

85 Annex9:GileadEligibleCountries

86 Annex10:MerckEligibleCountries

87 Annex11:SuggestedResourcesforFurtherInformation

88 Annex12:CompanyContacts

89 Annex13:TheClintonFoundationAntiretroviralPriceList

92 References

99 Abbreviations

Contents continued


BACkGROUND: ACCESS TO ANTIRETROVIRALS

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MSFiscurrentlysupportingcareandtreatmentformorethan154,000peoplein27countries.Bytheendof2008,atotaloffourmillionpeopleacrossthedevelopingworldwereonART.1

DeliveringARTtomillionsofpeopleindevelopingcountrieswasmadepossiblebecausetreatmentwasbroughtclosetowherepeoplelived,thepriceofmedicinescamedowndramatically,andtreatmentwassimplifiedandmademorepatient-friendly,withseveralmedicinescombinedintoonepill(knownasafixed-dosecombination,orFDC).Andinordertoaddresstheshortagesofmedicalstaffinmanycountries,tasksarebeingshifted,sothatnursesornurseaidescanperformmanyofthedutiespreviouslyreservedfordoctors.

Whiletheseachievementsrepresentimportantprogress,thecrisisisfarfromover.Untilrecentlyitwasestimatedthatalmost10millionpeopleareinimmediateneedoftreatment,atestamenttothepersistentemergency.2WiththerevisionoftheWorldHealthOrganization(WHO)guidelinesinlate20099,whichrecommend,inlinewithcurrentevidence,thattreatmentbeinitiatedearlierinapatient’sdiseaseprogression,thenumberofpatientsinneedofARTisexpectedbysometoincreasebyafurtherfivemillionto

around14millionpeople.3Thenumberofpeoplewhowillneedtreatmentby2030hasbeenprojectedtoreachasmanyas55million.4

Atthesametime,withgrowingnumbersofpatientsindevelopingcountrieshavingbeenontreatmentforfiveyearsorlonger,newchallengesareemergingtoensuretheirlong-termsurvival.Fortreatmenttobemostsuccessful,patientsneedtobemonitoredeffectivelyandhaveaccesstonewerandmorepotentdrugswhentheyinevitablydevelopresistanceorsideeffectstotheirmedicinesovertime.Butmostnewerdrugsareunaffordablebecauseofhighmonopolisticpricesandcrucialmonitoringtestsarenotadaptedforuseinresource-poorsettings.

However,theinternationalAIDSeffortisatacriticaljuncture,compromised

furtherbytheresponseofworldleaderstotheeconomiccrisis:thetwomainfundingsourcesforHIV/AIDSindevelopingcountries,theGlobalFundtoFightAIDS,TuberculosisandMalariaandtheU.S.President’sEmergencyPlanforAIDSRelief(PEPFAR),willnotbeabletosupportthetreatmentscale-upatitscurrentrategiveninsufficientdonorcommitment.TheGlobalFundisfacingasignificantfinancinggapandPEPFAR’sfundinglevelsareflat.187Barelyfouryearsafterworldleadersmetatthe2006UnitedNationsGeneralAssemblyandcommittedtouniversalaccesstoHIVprevention,treatmentandcare,politicalandfundingsupportiswaning.

ExtendingARVtreatmentindevelopingcountriestoallpeopleinneed,whileensuringpatientscansurvivewithHIVinthelong-term,willrequiremuchmoreinvestmentandpoliticalwill.

AIDS PROGRESS UNDER SIEGE: THE EMERGENCy IS FAR FROM OVER

HIV/AIDS is a lifelong disease, and although there is no cure, treatment with antiretroviral drugs (ARVs) prolongs and improves the quality of life.

AIDS treatment in developing countries began roughly a decade ago, mostly as small pilot projects and in the face of widespread scepticism about its feasibility in resource-poor settings. MSF was one of the first organisations to provide antiretroviral therapy (ART) in developing countries, starting with projects in Thailand and South Africa in 2000.152

‘�We’re�at�a�fork�in�the�road:�either�governments�summon�the�political�will�and�financial�resources�to�treat�AIDS�in�developing�countries,�or�current�funding�for�AIDS�treatment�stagnates,�which�means�patients�will�see�their�treatment�delayed,�deferred�and�denied.�It’s�a�question�of�choice:�if�they�don’t�help�us�treat�AIDS,�there�will�be�more�graves.’

Dr.�Tido�von�Schoen-Angerer,��Director�of�MSF’s�Campaign�for�Access�to�Essential�Medicines


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CHALLENGES: SECOND-CLASS AIDS TREATMENT

‘�The�number�of�people�

needing�HIV�treatment��

will�rise�over�the�next�

two�decades�and�so�will�

the�cost�of�treatment.�

This�is�because�better,�

more�effective�treatments�

have�come�on�the�market�

and�should�be�offered�to�

patients,�and�also�because,�

over�time,�more�people�will�

move�from�first-�to-second�

(and�later)�line�regimens,�

which�are�more�expensive.’�

The�Treatment�Timebomb�–�Report�of�the�Enquiry�of�the�UK�All�Party�Parliamentary�Group�on�AIDS�4

There is a growing disconnect between the AIDS treatment available to people in developed countries and to their counterparts in developing countries. In wealthy countries, AIDS now resembles a chronic disease, much like heart disease or diabetes, and patients generally have access to an increasing variety of treatment options once they inevitably develop drug resistance.5

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A) Move to a less toxic and more robust first-line regimen

Incontrast,peoplelivingwithHIV/AIDSindevelopingcountrieslargelyhaveaccesstoonlyonecombinationofmedicinesthatcausessignificantsideeffects,withfewornoalternativesforwhentheirtreatmentfails.AndtheyoungestpeoplelivingwithAIDScontinuetobeanafterthought–paediatrictreatmentstilllagsbehindthatforadults,asdoesthedevelopmentofappropriateARVsforchildren.

IfpeoplelivingwithHIV/AIDSaretobegiventhesameprospectsforsurvivalwhethertheyliveindevelopingcountriesorinwealthycountries,urgentactionmustbeundertakentoensureaccess:

•toalesstoxicfirst-lineregimen;

•tosecond-andthird-linetreatmentoptions,aspatientsdevelopresistance;

•tobetterandtimelydetectionoftreatmentfailure,throughviralloadtesting;and

•topaediatricAIDStreatmentoptions,whichmustbeprioritised,togetherwiththepreventionofmother-to-childtransmissionofthevirus.

Thefirstlineofdefencetohelpslow

thepaceatwhichpatientsneedto

switchtonewer,moreexpensiveARV

treatmentregimensisarobustfirst-line

drugcombinationwithfewsideeffects.

Today,themajorityofpeopleon

theirfirst-lineofARVsinlow-and

middle-incomecountriesreceivethe

combinationoflamivudine/stavudine/

nevirapine(3TC/d4T/NVP).6Thankstogenericcompetition,thisregimennowcostsUS$67perpatientperyear(ppy)–99%lessthan10yearsago.Thisdramaticpricedropwaspossiblebecauseofcompetitionamongmultiplegenericmanufacturersincountrieswherethesedrugswerenotpatented,suchasBrazil,ThailandandIndia(seegraph1).

Notwithstandingthedramaticpricedropoverthepastdecade,usingthisstandardcombinationcomesatahighmedicalcost.Thedrugstavudine(d4T)causesserioussideeffects,someintolerable,suchasperipheralneuropathy.Itcanalsoleadtolacticacidosis,whichinrarecasescanleadtodeath.Italsocausesstigmatisationbecauseoverlong-termtreatment,patientsdevelopeasilyrecognisablefacialwasting.


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Jun 00 Jun 02 Jun 03 Jun 06 Jul 07 Jul 08 Aug 09 Jun 10Dec 02 Dec 03 Apr 04 Jan 05 Jun 05Sept 01

US$

per p

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8000

6000

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Lowest Originator $10439






Brazil $2767

Hetero $295

Aurobindo $159Hetero $281

Cipla $132

Cipla $80 Aurobindo,Matrix & Cipla $67

Hetero $87

GRAPH �: GENERIC COMPETITION AS A CATALyST FOR PRICE REDUCTIONS. Thefallinthepriceoffirst-linecombinationsofstavudine(d4T),lamivudine(3TC),andnevirapine(NVP),since2000.

Stavudineisvirtuallynolongerusedinwealthycountries(in2006,forexample,fewerthan2%ofpatientsinSwitzerlandweretakingthedrug7).Patientsinthesecountriesareofferedbetter-toleratedalternatives,suchastenofovir(TDF)orzidovudine(AZT).Since2006,WHOhasrecommendedinitsHIV/AIDStreatmentguidelinesthattreatmentprovidersbeginmovingawayfromstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffects,towardstenofovirorzidovudine-containingregimens.8

ThiscallwasrepeatedinthelatestrecommendationsreleasedbyWHOinDecember2009forARTforHIVinadultsandadolescents,advisingcountriestodevelopaplantomovetowardstenofovirorzidovudine-basedfirst-lineregimens.9

Butuntilnow,thesignificantlyhighercostsofthesealternativeshavelargelypreventedthisswitchinmanydevelopingcountries.Better,less-toxicfirst-lineregimensarestillatbestnearlydoublethepriceofthestavudine-basedfirst-lineregimen.

However,therehasbeenanoteworthydownwardtrendinthepricesofless-toxicfirst-linecombinations.Thepriceoftenofovirhascomedownsignificantlyoverthepastfewyears,byalmost77%.ThismeansthatTDF-basedcombinationsarenownearlythesamepriceasthosecontainingzidovudine(seegraph2).Fixed-dosecombinationscontainingzidovudine(AZT/3TC/NVP)andthose

containingtenofovir(TDF/3TC/EFV)havebothfallen,by17%and59%respectivelyinthepastthreeyears.

Itisthankstogenericcompetitionthatthesepricesaresteadilycomingdown,andtheycanbeexpectedtofallfurtherasdemandincreases.Incountrieswherethedrugsarenotunderpatentorwherepatentsownerspermitsuchcompetition,theone-pill-once-a-daygenerictriplecombinationcontaining

tenofovir/lamivudine/efavirenz(TDF/3TC/EFV)isnowavailablefor$176ppy(seegraph2).Butinsomelowermiddle-incomecountries,patentownersdonotpermitaccesstogenericproducts,meaningthatcountrieshavetorelyonthe‘discounted’priceofferedbyoriginatorcompanies.Fortenofovir/emtricitabine/efavirenz(TDF/FTC/EFV),thismeansapricealmostsixtimesmoreexpensive,at$1,033ppy.

GRAPH �: THE PRICE OF NEWER, IMPROVED FIRST-LINE REGIMENS IN �0�0.Genericcompetitionhasallowednewer,improvedfirst-lineregimensrecommendedbyWHOtofallinprice,butinsomecountries,patentprotectionmeanspricesstayatunaffordablelevels.

Lowest generic price

AZT/3TC/NVP


TDF/3TC+NVP


AZT/3TC+EFV


TDF/3TC/EFV


TDF/FTC/EFV

Originator price for LMIC*

TDF/FTC/EFV

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1033

219176171141137

*LMIC–Lowermiddle-incomecountries(seeannex6)


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concern.Butthelong-termbenefitsofpatientsbeingabletotolerateandstayontheirfirstARVcombinationlongercanoutweighthecosts.AstudyinLesothoshowedthatusingageneric

tenofovir-basedregimenresultsinbetterqualityoflifeforpatientsascomparedtoastavudine-basedregimen.10Andwhileshiftingtreatmentprogrammestoanewfirst-lineregimenbringswithitclearlogisticalchallengesontopof

costconcerns,itiscriticalthattreatmentprovidersbeginmovingawayfromstavudineashasbeendoneforexampleinZambia,Lesotho,Guyana,SouthAfricaandBotswana.

DESIGN HIV DRUGS WITH DEVELOPING COUNTRy NEEDS IN MIND

With95%ofpeoplewithHIV/AIDSlivingindevelopingcountries,itisurgentthatresearchanddevelopmenttakeintoaccounttheparticularneedsofthesepopulations.Suchconsiderationsmustbesystematicallyintegratedintotheearlystagesofthedrugdevelopmentprocess.

Overthelastthreeyears,therehavebeensignificantadvancesinHIVmedicine,whichhaveledtoanumberofnewdrugsfromolderclasses,aswellasentirelynewtherapeuticclassesbeingapprovedforuse.ThenewdrugclasseshavedifferentmechanismsofactiontotargettheHIVvirus,providingpeoplelivingwithHIV/AIDSwithadditionaltreatmentoptions.

However,sinceARVsaredevelopedprimarilyfordevelopedcountrymarkets,datarelevanttoaddressthespecificneedsofpopulationsindevelopingcountries,suchaspregnantwomenorpeoplewhoalsoneedtotakedrugsfortuberculosisduetoco-infection,isnotobtainedinclinicaltrials.Afurtherexampleisthelackofknowledgeabouttheinteractionsbetweenantimalarialsandantiretrovirals,12eventhough80%ofpeoplelivingwithHIVliveinregionswheremalariaisendemic.13

Further,thereiscurrentlynosafetyandefficacydataforchildrenforthenewdrugsetravirine,maraviroc,orraltegravir.Forotherdrugstherearelimiteddata:forefavirenz(nodataforchildrenunderthreeyears),

atazanaviranddarunavir(nodataforchildrenundersixyears).ThisdespitethefactthattheU.S.FoodandDrugAdministration(FDA)hasincludedincentivesandobligationstoencouragesubmissionofdataforpaediatricusesince199714andtheEuropeanMedicinesAgency(EMA)followedsuitinJanuary2007.15

Theneedforhigh-techmonitoringcanalsoaffecttheavailabilityofantiretrovirals.Forinstance,theentryinhibitormaravirocrequiresacomplicateddiagnostictestcostingmorethanUS$1,900–afactormakingitsuseimpracticableandunaffordableindevelopingcountrycontextswhereevensimplelaboratorymonitoringisrarelyavailable.

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MSF


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LifelongAIDStreatmentrequiresconstantaccesstonewerandmorepotentdrugregimenswhenpatientsdevelopsideeffectsorresistancetotheirmedicinesovertime.Althoughresistanceisaninevitableelementoflong-termtreatment,itcanbedelayedbyusingdrugcombinationswithfewersideeffectstofacilitateadherence,andcanbelimitedbychangingtreatmentsoonafterviralsuppressionbeginstowane.NewWHOguidelinesonsecond-linefurthersimplifyandprioritisethechoiceofregimens.

DemandfornewerAIDSdrugsisgrowingfast.InoneofMSF’slongest-runningAIDStreatmentprogrammes,inKhayelitsha,SouthAfrica,14%ofpatientsontreatmentforfiveyearsneededtoswitchtoasecond-linedrugcombinationbecauseofvirologicalfailure.24And25%ofthosepatientswhoswitchedagaindevelopedvirologicalfailuretotheirsecond-lineregimenafurthertwoyearslater.188

B) SECURE ACCESS TO SECOND- AND THIRD–LINE REGIMENS

MSF’sKhayelitshadataprovidesawindowintothegrowingneedforaccesstonewerAIDSdrugregimensacrossthedevelopingworldinthecomingyears.Assomepatientsindevelopingcountrieshavealreadydevelopedresistancetotheirsecond-lineregimen,itiscrucialtosecurefurthertreatmentoptionsessentialtolong-termsurvival.However,thepriceofnewerregimensremainsamajorbarriertoaccess.

Themostaffordablesecond-lineregimenrecommendedbynewWHOguidelinesistodaypricedat$465(seegraph3).Thisismorethanthreetimesthemostaffordableoftheimprovedfirst-lineregimensrecommendedbyWHO.

DEATH AT THE DOORSTEP: THEMBISA’S STORy

‘I’m so worried now because I don’t know what is going to happen to me,’saysThembisaMkhosana,amotheroftwowholivesinKhayelitsha,SouthAfrica.ThembisadiscoveredshewasHIV-positivein2001andbeganreceivingARTthroughMSF’sclinictwoyearslater.Sherespondedwelltotreatmentandwasabletoreturntoworkandtakecareofherchildren.

Butaftershowingsignsoftreatmentfailurebecauseofdrugresistance,

ThembisawasswitchedtoasecondsetofARVs.Againshedevelopedresistance.ThembisanowneedsathirdsetofARVstokeepheralivebutthosenewerdrugsareunaffordable.‘If there’s no such thing that can help me, I know that I’m going to die,’saysThembisa.‘And then who is going to look after my children?’

Thembisaisbutoneofmanypatientswhonowneedaccesstonewerandmorepotent,butunaffordableARVregimens.

‘What we are seeing in Khayelitsha is what we will soon see throughout Africa if there is not a focused push for urgent change,’saysDr.EricGoemaere,MedicalCoordinatorforMSFinSouthAfrica.

GRAPH �: THE TREATMENT TIME BOMB: THE IMPACT OF SWITCHING TO SECOND- AND THIRD-LINE REGIMENS ON THE PRICE OF ARV TREATMENT. Changingapatient’sregimenbecauseofsideeffectsortheemergenceofresistancemeansrelyingonnewer,patented,andthereforemoreexpensivedrugs.Thepriceofapossiblethird-lineregimenmaycostatleast23timesmorethanthemostaffordablefirst-lineregimen,andclosetoseventimesmorethanthemostaffordablesecond-lineregimen.Patientsandtreatmentprovidersareonceagainfacedwiththeprospectofdrugsbeingpricedoutofreach.

*Atthetimeofgoingtopress,thereisnoTDF/3TC+ATV+rco-pack.TheClintonFoundation-negotiatedpriceoftheindividualcomponentsofthispackagecomesto$465.CFexpectstheco-packtobeavailablebytheendof2010.Atthatstageitspriceisexpectedtodropto$425.


AZT/3TC/NVP


TDF/3TC/EFV

Best CF priceTDF/3TC+ATV+r

Best CF priceAZT/3TC+ATV+r

RAL+DVR+r + etravirine

US$

per

pat

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yea

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3500

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2500

2000

1500

1000

500

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3204

465465*137 x3.4

first-linex23.4

second-linex7

possible third-line

176

Pricecomparisonsoffirst-lines,second-linesandpossiblethird-lines

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‘�Seeing�a�patient�that�you�

have�been�treating�since�

2003,�now�failing�on�her�

second�combination,�you�

feel,�as�a�nurse,�you�are�a�

failure.�We�are�feeling�like�

our�hands�are�tied.’�

Mpumi�Mantangana,�MSF�nurse��in�Khayelitsha,�South�Africa


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recommendationswhichforthefirsttimeraisestheneedfortreatmentoptionsafterfailureofsecond-linetherapy.Manystudiesareongoing,andthedrugslikelytohaveanti-HIVactivityinthird-lineregimensaredarunavir(boostedwithritonavir),etravirineandraltegravir.9

Becauseofpatentbarriers,genericcompetitiononthesemedicinesisseverelyhampered.UnlikewiththefirstgenerationofAIDSdrugs,patentsinkeyproducingcountriessuchasIndiapreventtheproductionofmuchmoreaffordablegenericversions:manyofthenewerARVswilllikelybeunderpatentinIndia,andseveralsuchasraltegravir,

maravirocoretravirinealreadyare.ThelackofcompetitionamonggenericmanufacturersmeansthatpricescannotbeexpectedtocomedownthewaytheydidforthefirstgenerationofARVs.

Thereisnogenericversionofetravirine,forexample.Itsmanufacturer,Tibotec,hasjustannounceda‘discounted’priceforSub-SaharanAfricaandleast-developedcountries,at$913ppy.Apotentialthird-lineregimencouldthusbeavailablefordevelopingcountriesattheprohibitivepriceof$3,204ppy(atbest,asthispriceappliestoonlyAfricaandleast-developedcountries).

Thereisnoroomforcomplacencyabouttheseprices.Formostpeoplewhoare

failingontheirsecond-linecombinationalready,thisunaffordablepricewillmeantheyalmostcertainlyonceagainfacedeath.

ItisimperativethatgovernmentsundertakemeasurestoensurethatpeopleinneedofnewerandmorepotentARVsarenotdeniedaccessbecauseofpatentbarriers.Thisincludes,butisnotlimitedto,theroutineuseofcompulsorylicensingandotherpublichealthsafeguardssetoutintheTRIPSAgreement(Trade-RelatedAspectsofIntellectualPropertyRights).TheplannedMedicinesPatentPoolforantiretroviralsisanimportantadditionalmechanismtoensurefutureavailabilityofaffordableessentialmedicines(seebox).

Whiletherehasbeenimportantprogressinscaling-uppaediatricAIDStreatmentoverthepastyear,childrencontinuetobeanafterthoughtwhenitcomestotreatmentanddevelopingappropriateandadaptedmedicinestomeettheirneeds.Furthermore,muchmoreeffortneedstobeplacedonpreventionofmother-to-childtransmission(PMTCT)ofthevirusinordertoeliminatetheseentirelyavoidableinfectionsinthefirstplace.

ThevastmajorityofchildrenwithHIV/AIDSareinfectedthroughtransmissionfromthemotherduringpregnancy,childbirthorbreastfeeding.PMTCThasbeensosuccessfulinwealthycountriesthatnearlynochildrenarenewlyinfectedwithAIDS.Butindevelopingcountries,nearly430,000newchildinfectionsoccurredin2008–atestamenttothefailuretoeffectivelyimplementsimplifiedandefficientPMTCTstrategiesthatcoulddramaticallyreducethenumberofchildinfections.16InthelatestWHOguidelineonPMTCTandinfantfeeding,moreoptionshavebeenrecommendedincludingtheprovisionoftripleARTtoallHIV-positivepregnantwomenandintroducingwaystoprotectthechildthroughoutthebreastfeedingperiod.76Thiswouldlessentheneedforpaediatrictreatment,ashasbeenseeninwealthycountries.

BecausetherearesofewchildrenwithHIV/AIDSinwealthycountries,thereisverylimitedinvestmentbythepharmaceuticalindustryintodevelopingappropriateandadaptedpaediatricARVs.

ItisnoteworthythattheavailablepaediatricFDCtabletsthatcomeindosesforvariouschildsizesareproducedmainlybygenericcompanies.

ThepriceofthepaediatricFDCd4T/3TC/NVP,at$53ppy,isfinallylower

thanthatforadults.ButthefactthatthefirstWHOprequalifiedpaediatricARVFDCbecameavailableonlyin2006,whiletheadultequivalenthasbeenavailablesince2001,reflectsthewayinwhichchildrenwithAIDSlagbehind.

C) PUT AN END TO THE NEGLECT OF CHILDREN LIVING WITH HIV/AIDS

DEVELOP SIMPLE DIAGNOSTIC AND MONITORING TOOLS FOR ADULTS AND CHILDREN

ItisvitallyimportanttobeabletodetectwhenapatientisnolongerrespondingtoART.Switchingsomeonetoanewerdrugcombinationtoolateortoosooncancompromisethetreatment’seffectiveness.

AtechnologyusedtodetecttheleveloftheAIDSvirusinpatients’blood–called‘viralload’testing–isthegoldstandard.However,itrequiresaccesstolaboratorieswithsophisticatedequipment,trainedstaffandthetransportofbloodsamples,allofwhichcanbecomplicatedorevenimpossibleinremotesettingsofpoorcountries.

Thereisanurgentneedforsimpleandeasy-to-usemonitoringteststhatcanbeusedonthespot,overcomingthesepracticalbarriers.Withoutaccesstosuchtests,manypatientsarebeingswitchedtooearlyortoolate,onlywhentheyappeartobegettingsickagainoncethevirushastakenholdanew.

Furthermore,HIV/AIDSdiagnosisininfantsisextremelydifficult.Inbabiesunder18monthsitcanonlybeconductedwiththeuseofacomplexDNA-baseddiagnostictestthatisexpensivetoconduct,alsorequiringtrainedpersonnelandaccesstosophisticatedlaboratoryequipment.Only15%ofchildrenborntomotherslivingwithHIVinlow-andmiddle-incomecountriesweretestedforHIVwithinthefirsttwomonthsoflife.6Thereisadesperateneedtodevelopasimplediagnostictestthatcanbeusedtodetectthevirusinyoungerinfantsonthespot,sothattreatmentcanbeinitiatedasearlyasnecessary.Earlyinfantdiagnosisiskeybecausewithouttreatment,halfthechildrenwilldiebeforetheageoftwo.

Untilnewtoolsexist,however,itisurgentfordonorsandtreatmentproviderstoensurethattheexistingdiagnostictechnologiesareimplementedaswidelyaspossible.


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Furthermore,ofthe22ARVsapproved

bytheU.S.FDAforadults,fivearenot

approvedforuseinchildrenandsixdo

notcomeinanypaediatricformulations.18

Whenpaediatricformulationsdoexist,

themajorityofthemcontinuetobe

ill-adaptedforuseinresource-poor

settings.Thismeanstheyeithercome

inpowderorsyrupform,withsomehaving

abittertaste,orneedingtobemixedwith

cleanwaterorrequiringrefrigeration,both

ofwhichcanbedifficulttocomebyin

manydevelopingcountrycontexts.

InApril2008,WHOrevisedits

paediatricARVtreatmentguidelines,

recommendingtheuseoftheprotease

inhibitorlopinavir/ritonavir(LPV/r)

forinfantsthathavebeenexposedto

nevirapine(NVP)directlyorthrough

theirmothers.130Thisrecommendation,

howeverjustified,meanstakinga

regimenincludinganLPV/rsyrup,which

FiercecompetitionamongmultiplegenericpharmaceuticalmanufacturersincountriessuchasIndiaandBrazil,wheremedicineswerenotpatented,iswhatbroughtthecostofAIDStreatmentdownby99%overthepastdecade,from$10,000to$67ppytoday.Indiahasthusbeencalledthe‘pharmacyofthedevelopingworld,’and,forexample,MSFsourcesmorethan80%oftheARVsusedinitsprojectsfromIndia.

AlackofpatentsinIndiaadditionallyfosteredtheproductionofFDCpills–crucialtothesimplificationoftreatmentthathasfosteredglobalscale-up–becausepatentsontheindividualcompoundsdidnotstandinthewayofcombiningthedrugs.

Butacrosstheglobe,increasedproductpatentingindevelopingcountriesisnowthreateningtheproductionofaffordable

genericversionsofnewermedicinesandthedevelopmentofbetterFDCs.InternationaltraderulesnowrequirethepatentingofmedicinesinkeyproducingcountrieslikeIndiaandBrazil,essentiallyeliminatingthekindofgenericcompetitionforthefuturethatbroughtpricesdowninthepast.

UndertheWorldTradeOrganization’sTRIPSAgreementandthe2001DohaDeclarationonTRIPSandPublicHealth,LDCsarenotrequiredtograntorenforcepatentsonpharmaceuticalsuntil2016.Thisperiodthereforeexpiresinbarelysixyears,afterwhichthesecountrieswillbefacingpatentbarriers.Considerationneedstobegiventohavethisperiodextended.

Tomorrow’sbattleforaccesstoaffordableARVswillneedtobefoughtinadifferentway.Toensurethatfundsstretchasfaraspossibletomeetthe

needs,policyactionsareneededtocontainthecostofdrugs,whileensuringqualitytreatmentforthelongterm.

ItwillrequireroutineuseofpublichealthsafeguardsinpatentlawsandofflexibilitiesintheTRIPSAgreement,andtheparticipationofpharmaceuticalcompanies–originatorandgeneric–innewmechanismstoboostaccess.

isnearly60%moreexpensivethana

liquidnevirapine-basedregimenandalso

requiresrefrigeration.

Atthesametime,thereisnoalternative

regimenoncethechildfailsthisregimen.

Thereisthusanurgentneedforthedevelopmentofchild-friendlydosesofheat-stableproteaseinhibitorsfortheyoungestpatients.Paediatricdosingstudiesforthenewer,morepotentdrugsmusturgentlybeconducted.

OVERCOMING CHALLENGES: STAVING OFF THE SECOND WAVE OF THE ACCESS CRISIS

‘�Reducing�the�costs�of�

drugs�could�enable�savings�

that�could�fund�access�to�

life-saving�treatment�for�

an�additional�one�million�

people�every�year,�even�

without�new�resources.’�

The�Treatment�Timebomb�–�Report�of�the�Enquiry�of�the�UK�All�Party�Parliamentary�Group�on�AIDS4

UNAFFORDABLE, AGAIN…

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•acountry’srighttodesignflexiblepatentlawsthatarefavourabletoaccesstomedicines;

•acountry’sright,whenessentialmedicinesarepatentedandunaffordable,toissuecompulsorylicensestoensureaccess;and

•pharmaceuticalcompaniesparticipatinginthenewMedicinesPatentPool,theinnovativemechanismrecentlyestablishedbyUNITAID.

WhileSection3(d)shouldhelpsafeguardagainstthegrantingoffrivolouspatents,thereisstillgreatconcernaboutnewerdrugs,inventedafter1995,whichcanbepatentedunderIndianlaw;severalsuchasetravirine,maraviroc,raltegraviralreadyare.

GenericproductionofthesenewerARVswillthusonlystartthroughlicensing–beitvoluntaryorcompulsory.

TheDohaDeclarationstressesthatcountrieshavetherighttodesignpatentlawsthatservetheinterestofpublichealth.

WhenIndiaamendeditspatentlawin2005,itincludedseveralkeysafeguardsincludingaprohibitiononthepatentingofinsignificantorminorimprovementsofknownmedicines.ThispartoftheIndiaPatentsActisknownasSection3(d).ItmeansthatpharmaceuticalcompaniesshouldnotbeabletoobtainpatentsinIndiaformedicinesthatarenotactualinventions,suchascombinationsorslightlymodifiedformulationsofexistingmedicines.Suchpatentapplicationsaredesignedtodelaygenericcompetitionthatcouldleadtolowerprices.

Forthefirsttime,acountrythusemphasisedstricterpatentabilitycriteriaforpharmaceuticalsandincludedprovisionsinitspatentlawstipulatingthatpatentsshouldonlybegrantedonmedicinesthataretrulynewandinnovative.

Thelawalsoallowsanyinterestedpartytoopposeapatentbeforeorafteritisgranted(‘pre-grant’and‘post-grant’oppositions).SuchoppositionshavebeenfiledinIndiabycivilsociety,patientgroupsandgenericcompaniesfromIndiaandBrazil,withthepositiveoutcomesthatseveralpatentsonkeyARVswererejectedbytheIndianpatentofficesonthegroundsthattheylackaninventivestepandfailtosatisfytherequirementsofSection3(d)ofthepatentlaw.

PUT A STOP TO FRIVOLOUS PATENTING

TheIndianPatentsAct,ifrigorouslyinterpreted,providesunderSection3(d)severalgroundsforrejectingapatentapplication,forinstanceifthepatentclaimedisonlyanewformofaknownpharmaceuticalsubstance.

In2006,theIndianpatentofficerejectedNovartis’patentapplicationforitsanti-cancerdrugimatinibmesylate(brandnameGleevec),onthegroundsthattheapplicationclaimsa‘newformofaknownsubstance’(Novartis’patentapplicationwasrelatedtoaparticularcrystalformofthesaltofimatinibmesylate).

Inessence,theIndianpatentofficewasapplyingthelaw,asapplicationsthatdonotclaimreal‘inventions’donotdeserveapatent.LikeNovartisinthisexample,manypatentapplicationsfiledbypharmaceuticalcompaniesareforanewuseofanolddrug,orsimplyforderivativesofolddrugsorcombinationsofolddrugs.

NovartislaunchedlegalproceedingschallengingtheconstitutionalityofSection3(d)ofIndia’sPatentsAct.ThispromptedMSFtolaunchthe‘DroptheCase’petitioninordertoprotectthe‘pharmacyofthedevelopingworld’.19NovartislostthiscaseinAugust2007whentheMadrasHighCourtupheldthepublichealthsafeguard.

ButNovartisisnotgivingup.HavinglostthebattletostrikedownSection3(d)ofIndia’sPatentsActalmostthreeyearsago,NovartishaslaunchedfreshlegalproceedingsinIndiatoweakenthiscriticalpublichealthsafeguard.TheSwissmultinationalpharmaceuticalcompanyhasfiledacasebeforetheIndianSupremeCourtinwhatcanbeconsideredthesecondpartoftheNovartiscase.

ThiscasewilldeterminethemannerinwhichSection3(d)willbeimplementedinIndia.

A) DESIGN FLExIBLE PATENT LAWS

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Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��

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THREE DOWN; MANy MORE TO GO: OPPOSING PATENTS IN INDIA IN THE NAME OF ACCESS TO AFFORDABLE MEDICINES

Sinceearly2006,theIndianNetworkofPeopleLivingwithHIV/AIDS,theDelhiNetworkofPositivePeopleandthePositiveWomen’sNetwork,togetherwithothercivilsocietygroupsinIndiaandbeyondhavefiledpre-grantoppositionsagainstthegrantingofpatentsonARVsrecommendedbyWHOforfirst-andsecond-linetreatment.Manyoftheseoppositionshavebeenfiledonthebasisofthepatentlaw’sSection3(d),whichprevents‘evergreening’ofknownmedicines.

In2006,GlaxoSmithKlinewithdrewitspatentapplicationforthelamivudine/zidovudinefixed-dosecombination,afterPLHAnetworksfiledapre-grantopposition.InJune2008,India’spatentofficedecidednottograntBoehringerIngelheimapatentforthenevirapinepaediatricsyrupafterapre-grantoppositionwasfiled.Thissetanimportantlegalprecedentandwasfollowedbytwofurthercrucialrejectionsin2009forpatentsonthekeyARVstenofoviranddarunavir,oneofthemostexpensiveARVstoday.

Whileseveralpatentapplicationsrelatingtotenofovir,darunavirandotherkeyARVsarestillpendingbeforethepatentoffice,theserejectionsrepresentamajorvictoryforaccess,asgenericmanufacturershavetakenuptheproductionofthesemedicinesovertimeensuringthelowestpossiblepricesforthesedrugs.ThesedecisionshighlightthesuccessandimportanceofSection3(d)andoppositionproceduresinIndia’spatentlawtosafeguardpublichealth.Othercountriesinneedofaccesstoaffordableessentialdrugsshouldbuildsimilarpublichealthsafeguardsintotheirownpatentlaw.

Whendrugsarepatented,andpharmaceuticalcompaniesfailtomakepatentedmedicinesavailableandaffordabletopatientsindevelopingcountries,governmentsshouldmakeuseoftheirright,underinternationaltradelaws,toissuecompulsorylicencestoensuregenericcompetition,unlesspatentownersagreetovoluntarilylicensetheirdrugonreasonableterms.Inbothcases,royaltiesarepaidtothepatentholder.

COMPULSORy LICENSING CompulsorylicensingisoneofthepublichealthsafeguardsenshrinedintheTRIPSAgreement,whichallowsagovernmenttooverrideapatentbyissuingalicencetoathirdpartytoproduceorimportthedrug.Issuingacompulsorylicence(CL)hasproventobringpricesdowndramaticallybyopeningupthemarkettocompetitionandtherebyincreasingaccess.

ThecaseoftheCLissuedbyThailandforLPV/rinJanuary2007clearlyillustratesthis.Overthecourseofoneyear,thepriceforLPV/rinmiddle-incomecountriesdecreasedbyasmuchas75%,from$2,200ppytounder$900inThailandand$550incountriesintheClintonFoundation

Consortium.Similarly,aCLissuedbyBrazilforefavirenzinMay2007broughtthecostforthedruginBrazildownbyalmost70%.

EventhoughissuingaCLisentirelyinlinewithWTOrules,countriesthattakethesteptypicallyfaceimmensedirectandindirectretaliatorymeasuresandpressurefromdevelopedcountrygovernmentsandthepharmaceuticalindustry.ThiscanservetodiscourageothercountriesthatareconsideringissuingCLs.Inaworldinwhichmedicinesarebecomingincreasinglypatented,CLs,includingthoseforexport,willbeacriticalmechanismtohelpensurethatessentialmedicinesareaffordableenoughforpeopletoaccessthemandcountriesmustfeelsupportedintheirrighttoincreaseaccesstoneededmedicinesfortheircitizens.

Thisalsomeansrevisingthecurrentmechanismdesignedtoallowtheexportingofmedicinesunderacompulsorylicencetocountrieswhichhavenomanufacturingcapacity,andthereforecannot‘simply’issueaCLandproducetheirowngenericmedicines.Thismechanism,knownastheAugust30Decision,wasadoptedbytheWorldTradeOrganization(WTO)in2003.

Billedasan‘expeditioussolution’thatwouldopenupaccesstomedicinesformillions,theDecisionisinfactcompletelyflawed.CanadawasoneofthefirstcountriestoenshrinetheDecisioninitsnationallaw–butittookfiveyearsfromthetimetheCanadianAccesstoMedicinesRegime(CAMR)becamelawforthefirstmedicinestobeexportedfromCanadaunderCLtoreachpatientsinAfrica.

Whilethefactthatthedrugsfinallymadeitisobviouslygoodnews,it’squiteclearthataprocessthattakessolong,forjustonedrug,forjustonecountryisnotanadequateresponse.Giventheglobalsituationwhere70%ofpatientsinneedofARTstilldonothaveaccesstotreatment,thisprocedureissimplynotuptothetask.

CanadiancivilsocietyiscurrentlypushingfortheCAMRtobereformed,buttheireffortsarebeingresistedbythepharmaceuticalindustry.ReformisneededattheinternationallevelattheWTO,andanin-depthreviewwillbeheldatthenextTRIPSCouncilmeetinginOctober.189YetanumberofdevelopedcountriescontinuetoopposeanyreviewoftheAugust30Decision,insistingthereisnotenoughevidencetoshowthatthemechanismisnotworking.190

B) kEEP THE DOOR OPEN FOR COMPETITION, DESPITE PATENTS

Médecins Sans Frontières | July 2010��

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Whenadrugispatentedinagivencountry,thepatentholdermaychoosetograntvoluntarylicences(VL)toothermanufacturers,allowingthemtoproduceandexportthedrug.WhentheseVLsareofferedtomultipleproducerswithinamarketorinseveralcountriesandarenotrestrictiveintermsofwherethelicenseesareallowedtoexportthedrug,theycanbeausefulwaytoincreaseaccess.

However,restrictiveVLscanalsoservemerelytoextendtheoriginatorcompany’scontroloveragivenmarket,stipulatingconditionssuchaswhichsourcetheactiveingredientmustbepurchasedfrom,aswellastowhichcountriesthedrugscanbeexported.SuchrestrictiveVLsultimatelydonotleadtotheunhinderedcompetitionthatallowspatientstobenefitfromthelowestpricespossible,nordotheyincreaseaccessinallcountrieswherethemedicinesareneeded.

Asanexample,U.S.pharmaceuticalcompany,GileadSciences,offeredvoluntarylicenceagreementsfortheproductionoftenofovirtoanyinterestedgenericmanufacturerinIndiawithanumberofclauses.TheVLagreementsstipulatethatthegenericmanufacturersmustpurchasetheactivepharmaceuticalingredientfromGileaditselforfromaGileadlicensee,insteadoffromacheapersource,andthatthemanufacturersmaynotexportthedrugtoseveralmiddle-incomecountries,includingBrazilandChina.Thismeansthatwhilecompetitionamongmultiplemanufacturers(licensees)withinIndiahasbeentakingplace,Gileadmaintainscontroloverwhichcountriesareabletobenefitfromtheselowerprices,oftenkeepingitselfasthesolesuppliersourceinthesecountries.

Crucially,allthiswasestablishedbyGileadatatimewhentheirpatent

applicationontenofovirwasstillawaitingarulingfromIndia’spatentoffice.In2006,Indiancivilsocietyorganisationshadfiledpre-grantoppositionstothepatentapplicationsonthegroundsthatthedrugconsistsofapreviously-knownsubstanceandisthereforenotpatentableunderIndia’sPatentsAct.

InSeptember2009,theIndianpatentofficesubsequentlydeclinedtograntapatentfortenofovirdisoproxilandtenofovirdisoproxilfumarateandinJuly,theBrazilianpatentofficedeclinedthepatentforTDF.GileadisnowpursinganewtactictomaintainitspatentonTDFbyfilingdivisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)intheBrazilianandIndianpatentoffices.

VOLUNTARy LICENSING

STOP THE DELIBERATE CONFUSION OF qUALITy GENERIC MEDICINES AND COUNTERFEIT MEDICINES

Overthepastfewyearstherehavebeenconcertedattemptstosubjectdevelopingcountriestomuchstricterenforcementofintellectualproperty(IP)ruleswhichgobeyondtheobligationsrequiredundertheTRIPSAgreementandthreatenthecontinuedsupplyofaffordablemedicinestodevelopingcountries.Aspartofthispush,thereareproposalstointroducenewproceduresandlawsagainst‘counterfeiting’–beitasnationallegislation,asapartoffreetradeagreements(FTAs),inmultipleinternationalforasuchastheWorldHealthOrganizationortheCouncilofEurope,orintheAnti-CounterfeitingTradeAgreement.Suchinitiativesthreatentohamperorpreventthetradeinaffordablegenericmedicinesbetweendevelopingcountries.

Crucially,theuseoftheterm‘counterfeiting’differsaccordingtothecontext:inintellectualproperty

law,itreferstotheprotectionofcommercialtrademarks,yetthewayinwhichithasbeencommonlyunderstoodbymanyinpublichealth,isasareferencetofakeorfalsely-labelledmedicinalproductsthatpresentapublichealththreat.Thisconfusionhasbeenexploitedandthepublichealthconcernsaboutfakeorfalsely-labelledmedicinesusedasanargumenttopushforstricterenforcementofintellectualproperty.Notonlydothesemeasuresfailtoaddressthepublichealthproblems,buttheyalsoactivelyinterferewithandthreatenaccesstomedicines.

ThedangersofoverbroadIPprotectionareillustratedbytherecentuseofEuropeanUnioncustomsrules,whichareusedtohelpenforceEUpatentsandtrademarks.Theseruleshaveinfactpreventedthetimelyaccesstolife-savingmedicines.Severalshipmentsofgenericmedicines-includingAIDS

drugs-havebeendetainedintransitthroughEuropeancountriesbasedonallegationsofIPinfringement,eventhoughtheyarenotprotectedbyIPrightsinthecountriesofexportorimport.ThishasaffectedthesupplyofessentialmedicinesfrommanufacturersinIndiatopatientsindevelopingcountriesinAfricaandLatinAmerica.TheEUcustomsrulesshouldbeamendedtopreventthisoccurringagain.

AnotherexampleistheKenyanAnti-CounterfeitingActwhichpassedinDecember2008,andwhichusesadefinitionofcounterfeitingsowidethatitincludesallproductsthatarecopiesofpatentedgoods.Thiswouldalsocoverquality-assuredandlegally-producedgenericmedicines.TheActthushasthepotentialtoseriouslyendangeraccesstogenericmedicines,suchasthoseusedbyMSFandothertreatmentprovidersinKenya.ItiscriticalthattheActberevised.ThreepeoplelivingwithHIV,

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Company-led‘access’schemeshaveproventobeminimallyeffective.Whilemostmultinationalcompaniestodaydoofferdiscountsthroughtieredpricing,thedatacontainedinUntanglingtheWebofAntiretroviralPricesclearlyshowsthatintheabsenceofgenericcompetitors,manufacturersenjoyingamonopolisticsituationdonotreducepricessignificantlyenoughtomakemedicinesaffordablefordevelopingcountries.Also,countriesthatareclassifiedas‘middle-income’suchasBrazil,Thailand,ChinaorColombia,areoftenleftoutofthediscountschemealtogetherorareofferedonlyminimaldiscounts.Primarilythethreatoflosingapatentorhavingapatentbarrierremovediswhatmakescompaniesrespondandreduceprices.Insomecases,genericcompetitionisonlypossiblethroughgovernmentsissuingcompulsorylicences.

Thereisonewaycompaniescouldacttomakeadifferencetoimproveaccesstomedicinesinthedevelopingworld,however.TheinternationaldrugpurchasefacilityUNITAIDhasrecentlyestablishedaMedicinesPatentPoolforantiretrovirals.Insteadofhavingpatentsactasbarriers,companies,researchersoruniversitieslicensethepatentson

theirinventionstooneentity:theMedicinesPatentPool.

Inthisway,anygenericcompanythatwantstousethepatentedinventionscanseekalicencefromthepool,underpre-determinedlicensingterms,inexchangeforthepaymentofroyaltiestothepatentholder.Thelicenseecouldthenproducegenericversionsofthepatentedinventionsandexportthemtocountriescoveredbythelicence.

Inordertoensureasufficientlyattractive,largemarketforpotentialproducers,thelicencesmustbevalidforawidegeographicalareawhichincludesalldevelopingcountries.Thiswouldresultincompetitionbetweenproducers,bringingdrugpricesdown.

supportedbypublichealthgroups,

havesuccessfullyobtainedaninterim

injunctiontostopkeypartsofthe

Actbeingimplemented,pendinga

fullhearingofajudicialreview,on

thegroundsthatthenewlegislation

contravenestheir‘righttolife’

undertheKenyanConstitution.At

the63rdWorldHealthAssemblyin

May2010theKenyanMinisterof

Healthannouncedpublicallythat

theMinistryofHealthhadnotbeen

consultedonthedraftlawwhich

hashamperedeffortstoimprove

accesstomedicineinthecountry.11,22

Therehavebeenrecentencouraging

statementsfromtheKenyan

Governmentthatthislegislation

mustnotaffectaccesstomedicines.

HowevertheActhasnotyet

beenamended.

Inaworryingtrend,thereareattemptstointroducesimilarlegislationinUganda.Publichealthorganisationsthereareconcernedthatthecountry’sdraftCounterfeitGoodsBill2009mayalsothreatenaccesstogenericmedicinesifpassedinitspresentform.

Onemajorproblemthatisnotaddressedbytheuseoftheexcessivelygeneralterm‘counterfeit’,andwhichMSFteamsfaceinmanycountries,isposedbysubstandarddrugs.Thesearedrugsfromoriginatorcompaniesaswellasfromgenericproducersthatdonotmeetinternationalstandardsofqualitysetforthem.

Todatethough,thefocusoftheresponsetothesequestionshasbeenplacedonprotectingcommercialinterests,ratherthanaddressingseriouspublichealthissues.

Thishasmeantdivertingattentionfromwhatneedstobedone.

Indirectresponsetotheseconcerns,WHOmemberstatesagreedattheWorldHealthAssemblyinMay2010tosetupanintergovernmentalworkinggrouptoensureWHOtakesapublichealthperspectiveinitseffortstoensuretheavailabilityofquality,safe,efficaciousandaffordablemedicines,excludingtradeandintellectualpropertyconsiderations.Itisimportantthattheworkinggroupactsquicklytoaddresstheseissues,andthatproposalsforgreaterprotectionofcommercialintereststhatthreatenaccesstomedicinesarerejected.

Tolearnmoreaboutthefatalconfusionbetweenlegitimategenericmedicinesandillegalfakes,pleasewatchMSF’sanimationathttp://vimeo.com/11709053

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C) POOL PATENTS AND TAkE THE PLUNGE FOR AFFORDABLE TREATMENT

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‘�Donors�have�been�shifting�their�focus�from�AIDS�to�other�diseases,�where�there�is�a�sense�that�more�lives�can�be�saved�more�cheaply.�At�a�time�when�we�should�be�scaling�up�to�meet�the�AIDS�challenge,�in�other�words,�we�are�dialling�back.�In�our�global�war�on�AIDS,�the�international�community�is�on�the�verge�of�snatching�defeat�from�the�jaws�of�victory.’�

UN�Secretary�General�Ban�Ki-Moon,�14�June�2010

1. Limitingtreatmentslotsmeanschoosingwholivesordies:Becauseoffundingcuts,treatmentprovidersarebeingforcedtoturnpeopleinneedoftreatmentawayfromclinicsinsomecountries,havingbeenforcedbylackoffundstoonlyenrollnewpatientsontreatmentwhenothersdieordefault.

2.Delayingordeferringtreatmentencouragestransmission,illnessanddeath:ProvidingARTearlierletspeoplelivehealthierlives,reducestheincidenceofopportunisticinfections,anddecreasestheneedforresultingcareandhospitalisation.Italsoreducesthenumberofpeoplelosttofollow-upbeforetheystarttreatment.Withincreasingevidencethattreatmentisprevention,failingtoprovidetreatmentearlieralsoallowsthevirustospread.

3.Failingtoensureastabledrugsupplymeansviralloadshootsthroughtheroof:Reducedfundingleadstovolatilityindrugsupplies,whichcanleadtodangeroustreatmentinterruptions.WithoutthevirusbeingconstantlysuppressedthroughARVs,peoplecanrapidlyfallillagainanddie,anddrug-resistantstrainscanspread.

4.BreakingthepromiseofARTmeanspeoplewon’tcomeforwardtogettested:Peoplecameforwardtogettestedbecausetheyknewtreatmentwasavailableshouldtheytestpositive.Ifpeopleinneedtotreatmentcometobelievethisisnolongertrue,thehard-wonprogressonencouragingpeopletoknowtheirstatuswillcomeundone,withpotentiallydisastrousramifications.

5.SlowingAIDSeffortsmeansthenumberofkidsinfectedwithHIVwillrise:Children’sneedshaveconsistentlylaggedbehindadultsforAIDStreatment.Badlyneededdiagnostictestsanddrugoptionsforchildrenwillbeevenlessofapriorityinareducedfundingenvironment.ImprovedWHO-recommendedprotocolstopreventtransmissionofthevirusfrommother-to-child(PMTCT)willalsolikelyfallbythewayside,meaningtheneedlessinfectionofnewbornchildren.

6.SlowingdowntheintegrationofHIVandTBcaremeanspatientswillslipthroughthecracks:TBremainsthenumberonekillerofpeoplelivingwithHIV/AIDS,andprovidingintegratedcareforbothTBandHIV/AIDSisthemosteffectivewaytotacklethisdualepidemic.Butsuchintegrationhasonlybarelybeguninendemiccountries,andwaningsupportforHIV/AIDScarewillslowitevenfurther.

7.Choosingbetweenmaternal&childhealthorAIDSmeansmakingafalsechoice:AIDSisthemainkillerofwomenofchildbearingageandover40%ofdeathsofchildrenunderfiveyearsinsixsouthernAfricancountriesarebecauseofAIDS.AddressingAIDScreatespositiveknock-oneffectsinotherhealthareas.Morefundingshouldbeallocatedtoglobalhealthratherthanwithdrawingsupportfromoneareatofundanother.

8.Callinganendtodecentralisationofcaremeanit’shardertoreachpeopleinurgentneed:BringingAIDStreatmentclosetowherepeoplelivereachesmorepeopleinneedandlowerstherateofpatientslostto

follow-up.ThisisaparticularlyeffectivewaytoscaleupARTinareasthatarehardhitbyseverehealthworkershortages.Butwithoutsupport,itwillnotbepossibletoexpandthissuccessfulmodel.

9.Continuingtousedrugswithmoresideeffectsmeansrelegatingpatientstosecond-classcare:WHOhasrecommendedthatless-toxicdrugsbeusedinfirst-linetreatment,aspartoftheefforttoclosethetreatmentgapbetweenrichandpoorcountries.Thismeanssubstitutingstavudine,withsignificantsideeffects,fortenofovir(TDF),orzidovudine.Despitepricesfalling,thecheapestTDF-containingregimenisstillmoreexpensivethanolderalternatives.However,usingTDFdecreasesthecostofmanagingsideeffectsthroughmedicalcareand/orhospitalisation,therebyprovingmorecost-effectiveinthelongrun.Theprovisionofless-toxicmedicinescannotbeprioritisediffundsareshort.

10.Cuttingbackonfundingfortreatmentmeanssacrificinglong-termsurvival:AIDSisalifelongdiseaseandpatientsinevitablyneedtobeswitchedtonewerregimensasdrugresistancedevelopsovertime.Buttreatmentfailureisahiddenproblembecauseofalackofaffordableandaccessibleviralloadtesting.Further,newermedicinesaremuchmoreexpensive.Thismeansthatpatientsarelesslikelytobeswitchedwhennecessary,andevenlesssowhenthereisreducedfundingforAIDStreatment.

Donors are walking away from AIDS when �0 million people are still waiting for treatment. Help us stop the U-turn on AIDS. http://aids�0�0.msf.org

AIDS TREATMENT DELAyED, DEFERRED, DENIED

The past decade is testimony to the fact that treating AIDS in developing countries is feasible, saves lives and rebuilds devastated communities. But donors are now starting to shift their support away from HIV/AIDS, and MSF has seen the tangible effects this funding retreat is already having: care rationed because of limited treatment slots, treatment scale-up halted for those in urgent need, and an even more distant promise of universal access.

The decade ahead of us should not be spent undoing the hard-won advances. The AIDS funding retreat will have the following consequences:


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TheMedicinesPatentPoolhasthepotentialtohelpincreaseaccesstoARVsinthreekeyareas:

1.Byfosteringcompetitionamongmultiplemanufacturers,bringingpricesdownfornewermedicinesandincreasingaccess,itwillhelpmitigatetheimpactoftheTRIPSpatentregime,especiallyforthenewerARVspatentedinmanufacturingcountriessuchasIndiaandBrazil;

2. Itwillhelpfacilitatethecreationofneededfixed-dosecombinations,whereotherwisepatentsontheindividualdrugcompoundsstandintheway;and

3. ItwillfurtherfacilitatethedevelopmentofpaediatricARVformulationsandcombinations,byeliminatingpatentbarriersindevelopingcountries.

MéDECINS SANS FRONTIèRES IS CALLING FOR ALL PATENTS ON THE FOLLOWING ANTIRETROVIRALS (AND COMBINATIONS THEREOF) TO BE PUT IN THE MEDICINES PATENT POOL:lopinavir, ritonavir (Abbott);

nevirapine, tipranavir (BoehringerIngelheim);

atazanavir, didanosine (Bristol-MyersSquibb);

emtricitabine, GS-9350, elvitegravir, tenofovir disoproxil fumarate (Gilead);

efavirenz, raltegravir (Merck);

SPI-452 (Sequoia);

darunavir, etravirine, rilpivirine(Tibotec/Johnson&Johnson);

abacavir, fosamprenavir, lamivudine, maraviroc, S/GSK1349572 (ViiV)

Atthesametime,stepsmustbeundertakentoensurethatpeopleindevelopingcountriesarereceivingtheoptimalmonitoringandtreatmentthatsupportstheirlong-termsurvival,comparabletotheircounterpartslivingwithHIV/AIDSinwealthycountries.Thismeanssecuringaccesstoneededmonitoringtools,whileprovidingpatientsbothwitharobustfirst-lineregimenthathasfewsideeffects,aswellasensuringtherearetreatmentoptionsforwhenpatientsshowsignsofdrugresistanceandneedtoswitchtoasecond-orthird-linecombination.

Althoughpricesforcertainkeynewermedicineshavecomedownsignificantlybecauseofcompetitionamonggenericmanufacturersand

increaseddemand,overallpricesfor

newerdrugsremainunaffordablefor

developingcountriesandoutofreach

ofnationaltreatmentprogrammes.

Countriesmustbesupportedintheir

useofflexibilitiesininternationaltrade

rulestohelpbringpricesofnewer

drugsdownmoresystematicallyand

speedily.Thisisnecessarysothatthe

growingnumberofpeopleinneedof

newerandmorepotentdrugshave

immediateaccessoncetheyrequire

them.Pharmaceuticalcompanies

shouldparticipateintheMedicines

PatentPool,sothatneededformulations

canbemadeavailabletodeveloping

countriesmoreswiftlyandatmuch

moreaffordableprices.

HIV/AIDSmustcontinuetobetreatedastheemergencyitis.FundinglevelsmustbeincreasedtotakeonthemassivetaskofprovidingsustainedAIDStreatmentindevelopingcountries.Newfinancingmechanisms,suchasfinancialtransactiontaxesincludingcurrencytransactionlevies,shouldbeintroducedtohelpraisemuchneededadditionalsustainableandpredictableresources,partofwhichmustbededicatedtoglobalhealth.TheworryingtrendoftreatmentprovidersneedingtoscalebackARTatatimewhentheyshouldbescalingupmustbecounteredwithsustainedandreaffirmedcommitmentbyleadersanddonorstouniversalaccesstoHIV/AIDStreatment.

Looking back upon the first decade of AIDS treatment in developing countries shows key successes. Four million people on treatment are alive today, many of whom would have died without ARVs long ago. The case has thus been proven that AIDS treatment is entirely feasible in resource-limited settings. However, with six out of 10 people in need of treatment still not receiving it and with projections of up to 50 million people in need of treatment in roughly 20 years, it is clear that treatment scale up must occur at a faster pace.

MSFhasidentifiedalistofmedicineswhosepatentsshouldbeincludedinthepool,andalistofneededfixed-dosecombinationsthatitishopedthepoolwillhelpdeliver.However,thepoolwillbevoluntary,socrucially,thesuccessofthepatentpooldependsoncompanies’

CONCLUSION

willingnesstoincludetheirpatentsinthepoolforuseinalldevelopingcountries,andongenericmanufacturers’interestinthoselicences.WiththeFoundationentrustedwithrunningthepatentpoolnowofficiallyestablished,companieshavenoexcusesnottoact.

Continued from page 13


qU

AL

ITy

ISSU

ES

ReadersandpurchaserswishingtoobtainmoreinformationaboutdrugqualityarethereforeencouragedtoconsulttheWHOListofPrequalifiedMedicinalProductswhichcontainstheproductsthat‘meetunifiedstandardsofquality,safetyandefficacyforHIV/AIDS,malariaandtuberculosismedicines.’

MorecommonlyknownastheWHOprequalificationlist,theprojectwasinitiatedbytheWHOanddevelopedincollaborationwithotherUnitedNationsorganisations,principallyforprocurementbyUNagencies.TheprojectevaluatespharmaceuticalmanufacturersandproductsaccordingtoWHO-recommendedstandardsofqualityandcompliancewithGoodManufacturingPractices.

WHO’sPrequalificationProgrammeisabenchmarkfortheidentificationofqualityessentialmedicinesandhassignificantlyimprovedaccesstoqualitymedicinesoverthepastyears.Akeyfactorofsuccesshasbeenthatfinancialsupporttonationalprogrammeshasbeendependentonpurchasingmedicinesrespectingclearqualityassurancecriteria.InthistheWHOPrequalificationProgrammehasplayedanimportantrole,providingguidancetopurchasersonthequalityofmedicinesandtherebycreatingapositivemarketdynamicwheremanufacturersstrivetoreachWHOstandardsinordertocomplywithprocurementpolicies.

TheGlobalFundtoFightAIDS,TuberculosisandMalariahasrecentlychangeditsqualityassurancepolicysothatGlobalFundgrantfundsmayonlybeusedtoprocureantiretrovirals,anti-tuberculosisandanti-malarialfinishedproductsthatareeitherprequalifiedbytheWHOPrequalificationProgramme,authorisedforusebyaStringentDrugRegulatoryAuthority(SRA),orrecommendedforusebyanExpertReviewPanel(ERP).

Unfortunately,themajorityofdonorstodaydonothavesufficientqualityassurancecriteria,givingawrongsignaltomanufacturersbyremovingtheincentivetocomplywithWHOnormsandstandards,andultimatelyendangeringpatients’healthincountrieswheretheregulatorysystemremainsweak.DonorsanddrugpurchasersshouldtakeheedfromtheGlobalFund’sexampleandmakesurethattheyimplementaneffectivequalityassurancepolicyformedicinesboughtonbehalfofdevelopingcountries.

qUALITy OF DRUGS IN THE DATA PROVIDED IN UNTANGLING THE WEBManufacturerswhohaveatleastoneWHOprequalifiedantiretroviralformulationwereinvitedtoparticipateinthispublication.

ButnotalltheproductslistedinthisreporthavebeenprequalifiedbyWHOandonlysomeofthemareusedby

MSFinitsownprojects.ProductsincludedintheListofPrequalifiedMedicinalProducts(asofApril2010),includingtheonesapprovedbyHealthCanada,theEuropeanMedicinesAgency(EMA)througharticle58,U.S.FDAortentativelyapprovedbyU.S.FDA,appearinboldinthetablesofdrugprices.

PleaseconsulttheWHOwebsite(http://mednet3.who.int/prequal)forthelatestlistofprequalifiedproductsandforinformationonthestatusofdossierassessment.

qUALITy ISSUESThis report is a pricing guide, and as such does not include detailed information about the quality of the products listed. However, quality is important and price should not be the only factor determining procurement decisions.


ME

TH

OD

OL

OG

y

AlloriginatorcompaniesmarketingARVswereincludedinthesurvey,butthelistofgenericproducersisbynomeansexhaustive.OnlygenericcompaniesthathaveatleastoneARVlistedontheWHOListofPrequalifiedMedicinalProductsonthedateoftheinitialrequestforinformationwereincludedinthispublication.TheinitialquestionnairesweresentinthemiddleofApril2010.

Onlygenericmanufacturerswhoprovidedpricesfortheirproductsareincludedinthisdocument.AspenPharmacarewasinvitedtocontributetothispublication;however,thecompanyhaschosennottoprovideprices,andassuchwillnotbeincludedinthisdocument.Similarly,MacleodsandEmcurehavechosennottoprovideinformationforthispublication.

SOME IMPORTANT PRELIMINARy REMARkS ON THE DATA PRESENTED IN THIS REPORT:

•TheinformationonpricesgiveninthispublicationonlyrelatestoARVs.Itdoesnotincludeothercostslinkedtoantiretroviraltreatment,suchasdiagnosis,monitoringortreatmentofopportunisticinfections.Forinformationonthepricesoftheseproducts,pleasereferto‘InternationalDrugPriceIndicatorGuide’19andforpaediatricdrugs,‘Sourcesandpricesofselectedmedicinesforchildren’.20

•Themanufacturersprovidethepriceslistedinthispublication.Thepricespaidbythepurchasermightbehigherbecauseofadd-ons(suchasimporttaxesanddistributionmark-ups),ormaybelowerafternegotiations.Thedocumentshouldnotbeviewedasamanufacturer’spricelist,andprocurementagentsareadvisedtocontactmanufacturersdirectlytoconfirmprices.

METHODOLOGy

•Companiesusedifferenttradeterms(knownasincoterms).21Thesetradetermsoutlinetheresponsibilitiesofthemanufacturerandpurchaserswithregardtotransport,internationalfreightandinsurancecosts.Additionalinformationanddefinitionsofincotermscanbefoundinthe‘Abbreviations’sectionattheendofthisguide.Pricesinthepublicationhavenotbeenadjustedtoincorporatethedifferentterms.In2005,theU.S.GeneralAccountabilityOfficedemonstratedthatthesedifferencesdonotunderminetheiressentialcomparability.

•Originatorandsomegenericcompanieshavedifferenteligibilitycriteriafordifferentialpricingforcountriesandentities,meaningnotallcountriesandentitiescanaccessthepricethatismentionedinthisguide.Thedifferentcategoriesofpricesaredetailedonthedrugprofilepages.MoredetailedinformationonthedifferenteligibilitycriteriaisprovidedinAnnexes2-10.

•TheClintonFoundation’sHealthAccessInitiativenegotiatespricesforARVsanddiagnostictestswithgenericcompaniesonbehalfofnationalAIDSprogrammesincludedintheirconsortium.TheClintonFoundationhasreachedagreementswithsevenARVmanufacturerstolowerthepricesof38differentARVformulations,bothpaediatricandadult.Thecurrentpricelist,asofApril2010,canbefoundinAnnex13.

•Informationonpatentsisonlyindicativeandshouldbecheckedwithnationalauthorities.Itshouldinnowayformthebasisofaprocurementdecision.

•AstheinformationontheWHOListofPrequalifiedMedicinesisupdatedregularly,thelistshouldbeconsultedforup-to-dateinformationregardingquality.http://apps.who.int/prequal/

Questionnaires were sent to both originator and generic companies manufacturing antiretrovirals (ARVs), requesting information on prices for developing countries, restrictions that apply to each of the prices quoted (eligibility criteria), and any additional specificity applicable to the quoted prices. The data were collected up to May 2010.

NOTE:AnonlineversionofUntanglingtheWebofAntiretroviralPriceReductionslaunchedinJanuary2010.TheonlineversionreproducesthefeaturesofUntanglingtheWebinaclear,user-friendlyandfree-flowingdesign.Itisupdatedregularly.

Youcanaccessitathttp://utw.msfaccess.org


HOW TO READ THE DRUG PROFILES

HO

W T

O R

EA

D T

HE

DR

UG

PR

OF

ILE

S

GENERAL INFORMATION:

Generalinformationonthehistoryoftheproduct,brandname,dateofapprovalbytheU.S.FDAandrelevantWHOguidance.

TABLE ON PRICE INFORMATION – DEVELOPING COUNTRy PRICES, AS qUOTED By COMPANIES

AllpricesarequotedinUnitedStatesDollars(US$).Currencyconversionsweremadeonthedaythepriceinformationwasreceivedusingthecurrencyconvertersitewww.oanda.com.

Theannualcostoftreatmentperpatientyear(ppy)hasbeencalculatedaccordingtotheWHOdosingschedules,8multiplyingtheunitprice(onetablet,capsuleormillilitre)bythenumberofunitsrequiredforthedailydose,andby365.Thepriceofthesmallestunit(i.e.pricepercapsule,tablet,etc.)isincludedinbrackets.WherenoWHOguidelinesexistforaproduct,thedosageusedistheU.S.FDAapproveddosage.23

Pricesareroundeduptothethirddecimalforunitpriceandtothenearestwholenumberforyearlypriceperpatient.

Forpaediatrictreatments,pricesarecalculatedfora10kgchildusingrecommendeddosingbasedonweightbands,aspertheWHOtreatmentguidelines.137Thisisanestimate,astheweightofachildincreasesduringanygivenyear.Whenitwasnotpossibletocalculatethedosefora10kgchild,onlytheunitpriceisindicated.ForpaediatricFDCs,thedosagesusedforthecalculationarethoserecommendedbythePaediatricAntiretroviralWorkingGroupatWHO.137

ACCESS TO PRICE DISCOUNTS – CATEGORIES � AND �

WhenoriginatorcompaniesofferdiscountedpricesonARVs,eachappliesdifferenteligibilitycriteria.Thismeansthatacountrythatiseligibleforapricediscountfromonecompanymaybeexcludedfromthelistofeligiblecountriesbyanothercompany.Inthisdocument,theterm‘firstcategory’or‘category1’isusedtodescribethosecountriesthatareeligibleforthemostdiscountedpriceofferedbyacompany.Theterm‘secondcategory’or‘category2’isusedtodescribecountriesthatarenoteligibleforthelowestpricesreservedforcategory1countries,butareneverthelessofferedadiscountbycompanies–crucially,thisdiscountisusuallyconsiderablysmallerthanthediscountofferedtocategory1countries.

Toknowwhetheracountryiseligibleforadiscountedpriceofferedbyagivencompany,ortofindoutinwhichcategoryagivencountryisplacedbydifferentcompanies,pleaserefertotheannexes.

TheWHOListofPrequalifiedMedicinalProductsisalistofmanufacturersandsupplierswhomeetunifiedstandardsofquality,safetyandefficacyforHIV/AIDS,malariaandtuberculosismedicines.ProductsincludedintheWHOListofPrequalifiedMedicinalProductsforAntiretrovirals(asofApril2010)areinboldinthetablesofdrugprices.

ReadersandpurchaserswishingtoobtainmoreinformationaboutthequalityofARVsareencouragedtoconsulttheWHOPrequalificationProgramwebsiteasthislistisupdatedregularly(http://apps.who.int/prequal/).

TheClintonFoundation’sHIV/AIDSInitiativenegotiateswithseveralmanufacturersforreducedpricesforalmost38differentARVformulationsforcountriesintheirpooledprocurementconsortium.Manufacturerswhohaveaproductincludedinthemostrecentpriceannouncementareindicatedbya(CF)intheheaderofthetable.FurtherdetailsofthespecificsoftheproductcanbefoundinAnnex13.

PRICE CHANGES OVER TIME – CHART ON THE EVOLUTION OF THE LOWEST PRICE qUOTED FOR DEVELOPING COUNTRIES:

Thischartshowsthepriceevolutionovertime,forbothoriginatorandgenericproducts,asquotedtoMSFforthepurposeofthisdocumentsince2001.

IfagenericproductincludedintheWHOListofPrequalifiedMedicinalProductsisavailable,thegraphshowsthelowest-pricedgenericproductthatisincludedinthelist.IfnogenericproductisincludedintheWHOListofPrequalifiedMedicinalProducts,thelowest-pricedproductisconsideredinthegraph,regardlessofqualitystatus.

SPOTLIGHT ON ACCESS ISSUES – A LOOk AT PATENTS AND PAEDIATRICS

Themostsalientissuesrelatedtoaccesstoeachproductissummarisedhere.Thefocusisontheavailabilityofproducts,theiraffordabilityandtheiradaptabilityforthedevelopingworld.Specialcommenthasbeenincludedwhenappropriatewithregardtopatentsandpaediatrics.

There are separate drug profiles for each of the single antiretrovirals (ARVs), fixed-dose combinations (FDCs) and co-packs containing two or three ARVs. Each drug profile contains the following sections:


MARAVIROC ( MVC )M

AR

AV

IRO

C ( M

VC

)E

NT

Ry

INH

IBIT

OR

GENERAL INFORMATION

•Therapeuticclass:chemokineco-receptor5(CCR5)antagonist(entryinhibitor).

•NotcurrentlyincludedinWHOguidelines.

•Indicatedfortreatment-experiencedadultpatientsinfectedwithonlyCCR5tropicHIV-1detectablestrains,whohaveevidenceofviralreplicationandHIV-1strainsresistanttomultipleantiretroviralagents.25

•Originatorcompanyandproductbrandname:Pfizer,Selzentry.InApril2009,PfizerandGlaxoSmithKlinejointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):August2007.17

•NotincludedintheWHOModelListofEssentialMedicines(EML).26

•ThebasicpatentwasappliedforbyPfizerinDecember199927andisduetoexpirein2019.InMay2001,Pfizerappliedforanadditionalpatentmorespecificallyrelatedtocrystallinemaraviroc.28

PRICE INFORMATIONViiV was invited to contribute a price for this publication and has communicated it does not offer a reduced price for developing countries.

SPOTLIGHT ON ACCESS ISSUES

Maraviroc(MVC)isclassedasaCCR5co-receptorantagonistthattargetsthepenetrationofcellsbytheHIVvirus.Thisdrugoptionispredominatelyusedinthedevelopedworldas‘salvagetherapy’forpatientswhoarealreadyresistanttomultipledrugclasses.Notallpatientswillbenefitfromthisdrug,asonlysomeHIVvirusesusethisCCR5co-receptor.

Therecommendationisforpatientstohaveatropismtesttolookforthisco-receptorpriortotreatment.Indevelopingcountries,wherebasiclaboratorymonitoringisnotalwaysavailable,therealityofthistypeoftestingbeingavailableislimited.

Today,thistestisnotwidelyavailableandisexpensive,atapproximatelyUS$1,900.29

ViiVwasinvitedtocontributeapriceforthispublicationandhascommunicateditdoesnotofferareducedpricefordevelopingcountries.

PatentsPfizerobtainedapatentinIndiain2007.30

ThispatentblocksthemanufactureofgenericformulationsofMVCinIndia,limitingthemuch-neededcompetitionthathistoricallyhasbeenshowntoleadtopricereductions.

PfizerhasappliedforproductpatentsandpatentsforthecrystalforminBrazil,SouthAfrica,India,China,ARIPO31andOAPIcountries.32

Todate,patentsonthecrystalformhavebeengrantedinIndia,China,andARIPOandOAPIcountries.

PaediatricsThesafetyandefficacyofMVCinpatientsunder16yearsofagehavenotbeenestablished.

�0 Médecins Sans Frontières | July 2010

ENFUVIRTIDEE

NF

UV

IRT

IDE

FU

SIO

N I

NH

IBIT

OR

GENERAL INFORMATION

•Therapeuticclass:fusioninhibitor.


•Indicatedfortreatment-experiencedadultpatientswhohaveevidenceofviralHIV-1replicationdespiteongoingantiretroviraltherapy.33

•Originatorcompaniesandproductbrandname:RocheandTrimeris,Fuzeon.

•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):March2003.17


•ThebasicpatentonenfuvirtidewasappliedforbyDukeUniversityinJune1994,34andisduetoexpirein2014.DukeresearchersfoundedthepharmaceuticalcompanyTrimeris,

whichbegandevelopmentofenfuvirtide(previouslycalledT-20)in1996.In1999,TrimerisenteredintopartnershipwithHoffmann-LaRochetocompletethedevelopmentofthedrug.Chironalsoownspatentsrelatedtoprocessesforproducingenfuvirtide,35whichexpiredin2005,butprotectionhasbeenextendeduntil2010insomeEuropeancountries.AlicensingagreementwasestablishedbetweenRocheandChironin2004.36

PRICE INFORMATIONRoche was invited to contribute a price for this publication and has communicated it does not offer a lower price for developing countries and is not planning to offer one in the future.


Enfuvirtidewasthefirstdrugdevelopedinthefusioninhibitorclass.ThenovelmechanismofactionpreventsthepenetrationoftargetcellsbytheHIVvirus.Thisnewdrugoptionispredominatelyusedinthedevelopedworldas‘salvagetherapy’forpatientswhoarealreadyresistanttomultipleantiretroviralagents.

Enfuvirtideisformulatedasaninjectionandrequiresthepatientorcaregivertolearnthetechniqueofreconstitutingpowdervialswithsterilewater.Sincethevialsareformulatedforsingleuse,itrequiresthepatientorcaregivertoaccuratelysyringeouttherequired

doseandvolume.Thisisnotadaptedforuseinresource-limitedsettings,andthecurrentpriceinthedevelopedworldofnearlyUS$25,000perpatientperyearisprohibitiveformanydevelopingcountriesthatmayhaveaneedforthisproduct.37

InBrazil,enfuvirtideisavailableat$12,812ppy.129

Rochewasinvitedtocontributeapriceforthispublicationandhascommunicateditdoesnotofferalowerpricefordevelopingcountriesandisnotplanningtoofferoneinthefuture.

PatentsTrimerisfiledforpatentsrelatedtomethodsforsynthesizingenfuvirtideindevelopingcountriessuchasChinaandBrazil,whichmayrununtil2019.38

ThepatentwasgrantedinChina.39

PaediatricsThedrugisapprovedforuseinchildrenoversixyearsofage.


RALTEGRAVIR ( RAL )R

ALT

EG

RA

VIR

( RA

L )

INT

EG

RA

SE

INH

IBIT

OR

GENERAL INFORMATION

•Therapeuticclass:integraseinhibitor.

•ListedintheWHOguidelineaspotentialthird-linedrug.8

•Indicatedfortreatment-experiencedadultpatientswhohaveevidenceofviralreplicationandHIV-1strainsresistanttomultipleantiretroviralagents.40

•Originatorcompanyandproductbrandname:Merck,Isentress.

•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):October2007.17


•Worldsalesoforiginatorproduct:2009:US$752million41;2008:$361million;2007:$41million.42

•ThebasicpatentwasappliedforinOctober2002bytheInstituteforResearchinMolecularBiology(IRBM),Pomezia,Italy,oneofMerck’sresearchsites.43Thepatentisduetoexpirein2022.In2005,MerckandIRBMappliedforanotherpatentonthepotassiumsaltofRALwhichcanrunupto2025.44

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.

Dailydose

Merck

Category1countries Category2countries

Whocanaccessthisprice? Seeannex2&annex10

RAL400mgtablet 21113(1.525)

NotAvailable


Raltegravir(RAL)isthefirstofanewclassofdrugs(integraseinhibitors),whichhasanovelmechanismofactionandnoapparentcross-resistancewithotherARVs.

RAL,unlikemostproteaseinhibitors(PIs),doesnotrequireboostingwithritonavir(RTV).Thisnewdrugoptionwillbeveryimportantforpatientswhoaretreatment-experiencedandmayalreadyberesistanttomultipleantiretroviralagents.

InDecember2009,WHOreleasednewrecommendationswhichforthefirsttimecallforathird-linetherapy.Ashumanstudiesareongoing,thedrugslikelytohaveanti-HIVactivityinthird-lineregimensareboosteddarunavir,etravirineandraltegravir.9

Thereisnogenericraltegraviravailable.

RALpricingforcategory1countries(seeannex10)isextremelyhighandunaffordablefordevelopingcountries.RALpricingforcategory2countriesisstillunknown.InBrazil,however,raltegravirisalreadyincludedinthenationaltreatmentguidelinesandaround3,000patientsareonraltegravirinthecountry.Thecostperpatientperyearstandsat$5,870.129

PatentsMerckandIRBMappliedforpatentsinmanydevelopingcountrieswithgenericdrugmanufacturingcapacity,suchasBrazil,China,IndiaandSouthAfrica.IRBMwasgrantedapatentinIndiainDecember200745whichwillexpirein2022.

Genericcompetitiontoreducethepriceofthemedicinewillthereforeonlybepossiblethroughvoluntarylicencesissuedbythepatentholder,orthroughcompulsorylicencesissuedbythegovernment.

PaediatricsThesafetyandefficacyofRALinpatientsunder16yearsofagehavenotbeenestablished.Paediatricstudiesareongoinginchildrenfromfourweeksold.

�� Médecins Sans Frontières | July 2010

EFAVIRENZ ( EFV )E

FA

VIR

EN

Z (

EF

V )

NO

N-N

UC

LE

OSID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

IN

HIB

ITO

RS (

NN

RT

I )

GENERAL INFORMATION

•Therapeuticclass:non-nucleosidereversetranscriptaseinhibitor(NNRTI).

•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.18,137

•Originatorcompaniesandproductbrandnames:Bristol-MyersSquibb(BMS),Sustiva;orMerck,Stocrin.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):September1998.17

•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26

•Worldsalesoforiginatorproduct:2009:US$1.277billion;2008:$1.149billion;2007:$956million;2006:$791million;

2005:$680million;2004:$621million;and2003:$544million.46,47,48,49,50

•ThebasicpatentonEFVwasfiledin1993byMerck,andisduetoexpirein2013.51Subsequently,Merckfiledforpatentapplicationsrelatedtocrystallizedforms,duetoexpirein2018.52

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/capsule/suspensiondose.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dec 02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

500

450

400

350

300

250

200

150

100

50

0

lowest originator price

generic priceEFV 600mg tablet

462

61

346

237

Dailydose

Merck

Aurobindo(CF) Cipla(CF) Hetero Matrix(CF) Ranbaxy Strides(CF)Category1countries

Category2countries

Whocanaccessthisprice?

Seeannex2&annex10 Norestrictions

EFV30mg/mlsuspension

- (0.094/ml) (0.151/ml)

EFV50mgcapsule - (0.083)

EFV50mgtablet - (0.120) (0.210) (0.083)

EFV100mgcapsule - (0.150)

EFV200mgcapsule 3 130 (0.119)

134 (0.122)

152(0.139)

118 (0.108)

EFV200mgtablet 3394 (0.360)

821 (0.750)

146 (0.133)

110 (0.100)

EFV600mgtablet 1237 ( 0.650)

657 (1.800)

73 (0.200)

79 (0.217)

82 (0.225)

61 (0.167)

91 (0.250)

62 (0.170)

(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.SeeAnnex13fordetails.

Evolution of the lowest price quoted for developing countries since �00�:

AsofApril2010,thereweresevengenericsourcesofEFV600mgtabletlistedontheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Since2002,theoriginatorpricehasdecreasedby32%,whilegenericpriceshavedroppedby87%.


EFA

VIR

EN

Z ( E

FV

)N

ON

-NU

CL

EO

SID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

INH

IBIT

OR

S ( N

NR

TI )


Efavirenz(EFV)isakeydrugforfirst-linetreatment,asitisverypotent,withonce-dailydosing,andiswell-tolerated.

Initsnew2010guidelines,WHOrecommendstheuseofEFV-incombinationwithtwoNRTIs,oneofwhichshouldbezidovudine(AZT)ortenofovir(TDF)–asapreferredfirst-lineantiretroviraltreatment.9

EFVisalsorecommendedasthepreferredNNRTIforpatientsstartingARTwhileontuberculosistreatment.Rifampicin,oneofthemaindrugsusedtotreatTB,interactswithnevirapine(NVP),resultinginlowerbloodlevelsofNVP.EFV,however,doesnothavethesamedegreeofinteraction,andcanbeusedasanalternative.

Itsprice,however,remainshigh,particularlyforcountriesincludedinMerck’ssecondpricingtier(seeannex10),wherethepriceofEFV600mgtabletexceedsbymorethan10timesthepriceofthegenericversion.

Merckphasedoutthe200mgand50mgcapsuleformulations,whichhavebeenreplacedbytablets.

Patents

GenericcompetitionfromanumberofIndianmanufacturershasbroughtthepriceofEFVdownsignificantly.However,EFVremainsexpensiveincountrieswhereMerckholdspatentsthatblocktheproductionandsaleofgenerics.

IncountrieswhereEFVispatented,governmentsandcivilsocietygroupshavetakenvariousmeasurestoensuregenericcompetitionandlowerprices,including:

•InNovember2006,ThailandissuedacompulsorylicencetoimportgenericversionsofEFVfromIndia.Asaresult,theThaigovernmentisnowpurchasingEFVatUS$106perpatientperyear(ppy),whichisconsiderablylowerthanthepreviouspriceof$511ppy.53,54

•InMay2007,Brazil,afternumerousunsuccessfulnegotiationswithMerck,issuedacompulsorylicencetoimportmoreaffordablegenericversionsofEFVfromIndia.Atthetime,thepriceofEFVinBrazilwas$580ppyandhadnotchangedsince2003.Afterthecompulsorylicence,BrazilbegantoimportagenericversionprequalifiedbyWHOfor$190ppy.InFebruary2009,thepublicmanufacturerFarmanguinhos(Fiocruz)launchedthenationalgenericversionforuseintheBrazilianhealthsystem.55

•InSouthAfrica,Merck’srefusaltoallowsufficientgenericcompetitioncontributedsignificantlytothehighpriceofthedrug.ThisledtheAIDSLawProject(ALP),actingonbehalfoftheTreatmentActionCampaign(TAC),tofileacomplaintbeforetheCompetitionCommissioninNovember2007.Asaresult,Merckrecentlyagreedtolicenseitsproducttootherproducers,openingtheopportunityforgenericcompetitioninSouthAfrica,wheresixsuppliersnowmarketefavirenzorefavirenz–containingcombinationproducts.56

•InIndia,apatentfortheprocessofpreparingform1ofcrystallineEFVwasgrantedinJune2005.57EventhoughMerckdoesnotholdaproductpatentforEFV,thisrecentlygrantedprocesspatent

appearstoprotectakeyprocessformanufacturingEFV,andcouldthereforehaveanimpactongenericproductionofEFVinIndia.ThispatenthasthereforebeenopposedbyIndiancivilsocietyorganisationsusingthepost-grantoppositionproceduresenshrinedinIndia’spatentlaw.58

Inaddition,Gilead59andBMShavefiledpatentapplicationsrelatedtocombinationsofEFVwithotherARVs.Inparticular,BMS’seffortstoreceiveapatentfortheonce-a-daypillEFV/FTC/TDF60willhaveanimpactonaccesstoimprovedfirst-lineARVtreatmentinthedevelopingworld.InIndia,thepatentofficehasalreadyrejectedGilead’sapplication,61ascombinationsofknownmoleculesarenotpatentableunderIndia’spatentlaw.

PaediatricsDespitehavingreceivedU.S.FDAapprovalforuseinadultsin1998,thereisstillnoestablisheddosingofEFVforchildrenlessthanthreeyearsofage.ThereisanurgentneedtoestablishthedosingofEFVforthisagegroup.

Inearly2008,BMS,whichmarketsEFVinEurope,discontinuedthemanufactureofthe100mgcapsule,furtherlimitingoptionsforpaediatricpatients.Theoralsolution,whileallowingmoreflexibilityindosing,mustbediscarded30daysafterbeingopened,andisnotinterchangeableonamgpermgbasiswiththesoliddosageforms.Thebioavailabilityoftheoralsolutionislessthan70%oftheoraldosageforms,andhencealargerdoseisrequiredtoobtainthesamebloodlevels.


ETRAVIRINE (ETV)E

TR

AV

IRIN

E (

ET

V)

NO

N-N

UC

LE

OSID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

IN

HIB

ITO

RS (

NN

RT

I )

GENERAL INFORMATION


•ListedintheWHOguidelineaspotentialthird-linedrug.8

•ApprovedbyU.S.FoodandDrugAdministration(FDA)fortreatment-experiencedadultpatientswhohaveevidenceofresistancetoanNNRTIandotherantiretroviralagents.62


InDecember2009,WHOreleasednewrecommendationswhichforthefirsttimecallfortheneedforthird-linetherapy.Asmanystudiesareongoing,thedrugslikelytohaveanti-HIVactivityinthird-lineregimensareboosteddarunavir,etravirineandraltegravir.9

EtravirinewasapprovedbytheU.S.FDAinJanuary2008,andreceivedmarketingapprovalbytheEMAinAugust2008.Ithasnotyetbeenapprovedbyanydevelopingcountryhealthauthority.However,theproductisavailablethroughapre-approvalaccessprogramwhichismanagedbyAspenPharmacare.

•Originatorcompanyandproductbrandname:Tibotec,Intelence.

•FirstapprovedbytheU.S.FDA:January2008.17


•ThebasicpatentonetravirinewasappliedforbyJanssenPharmaceuticain1999andisduetoexpirein2019.63In2006,Tibotecappliedforsubsequentpatentsrelatedtonovelseriesofbisarylsubstitutedpyrimidinederivatives.BothJanssenPharmaceuticaandTibotecarenowpartofJohnson&Johnson.64,65


ThepriceofetravirinehasnowbeenrevealedforthefirsttimebyTibotec.AtUS$913ppy,thispriceisprohibitiveforthedevelopingcountries.Thereisnogenericversionofthisdrugavailable.

PatentsPatentshavebeenappliedforwidelyinthedevelopingworld,includinginAfrica.JanssenPharmaceuticaobtainedthemoleculepatentinIndia66andChina.39

Thispatentwillblockthedevelopmentofgenericformulationsofetravirine,unlesslicences–voluntaryorcompulsory-areissuedtogenericcompaniesforthemanufactureofaffordableversionsofthedrug.

PaediatricsEtravirineisnotapprovedforuseinchildrentoday.AwaiverofpaediatricstudiesfrombirthtotwomonthswasgrantedbytheEMAongroundsthatthemedicinedoesnotrepresentsignificanttherapeuticbenefitoverexistingtreatments.67

Dailydose Tibotec

Whocanaccessthisprice? Seeannex2

ETV100mgtablet 4913(0.625)


NEVIRAPINE ( NVP )N

EV

IRA

PIN

E ( N

VP

)N

ON

-NU

CL

EO

SID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

INH

IBIT

OR

S ( N

NR

TI )

GENERAL INFORMATION



•Originatorcompanyandproductbrandname:BoehringerIngelheim(BI),Viramune.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):June1996.17


AsofApril2010,therewere10genericsourcesofNVP200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Whileitwasapositiveresultthattheoriginatorcompanydroppeditspriceby50%in2007,thegenericpricehasdecreasedbyalmost80%since2001,andtodayisapproximately16%oftheoriginatorprice.

Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

US$

pp

y

Month/Year

500

450

400

350

300

250

200

150

100

50

0Jun10


generic priceNVP 200mg tablet

438

150

219

34

•Includedinthe16theditionof

theWHOModelListofEssential

Medicines(EML).26

•Worldsalesoforiginatorproduct:

2007:US$412million;2006:

$370million;2005:$386million;

2004:$378million.68,69,70,71

After2007,therearenosales

figuresquotedinthecompany’s

annualreport.

•ThebasicpatentsonNVPwereappliedforbyBIinNovember1990,andareduetoexpireinNovember2010.72BIalsoappliedforapatentonthehemihydrateformofNVP,usedinthesuspensionin1998,whichisduetoexpire2018.73Additionally,BIappliedforapatentontheextended-releaseformulationofnevirapinein2008,whichisduetoexpirein2028.74

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/suspensiondose.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

BI

Aurobindo(CF) Cipla(CF) Hetero(CF) Huahai Matrix(CF) Ranbaxy(CF) StridesCategory1countries

Category2countries


Seeannex2 Norestrictions

NVP10mg/mlsuspension

20ml380 (0.052/ml)

533 (0.073/ml)

66 (0.009/ml)

73 (0.010/ml)

NVP200mgtablet

2219 (0.300)

438 (0.600)

39 (0.054)

34 (0.046)

37 (0.050)

34 (0.047)

39 (0.054)

39 (0.053)

37 (0.050)

Continued overleaf



NE

VIR

AP

INE

( N

VP

)N

ON

-NU

CL

EO

SID

E R

EV

ER

SE

TR

AN

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TA

SE

IN

HIB

ITO

RS (

NN

RT

I )


Nevirapine(NVP)isawidely-usedARV,predominatelyinfirst-lineregimens.Ithasbeenanimportantcomponentofthefixed-dosecombinationsthathavefosteredtreatmentscale-upinresource-limitedsettings.

ThepriceofNVPhasdecreaseddramaticallyoverthepastyearsasaresultofgenericcompetition.

PatentsBoehringerIngelheim(BI)hasobtainedthebasicpatentonNVPinseveraldevelopingcountries,butnopatentcouldbeobtainedincountriessuchasIndia,Brazil,ChinaorThailand,whichwerenotgrantingpatentsonmedicinesatthetime.Manydevelopingcountries,whereNVPisunderpatent,importgenericversionsofNVPbymakinguseofTRIPSflexibilities.

However,afterIndiaintroducedpatentprotectionforpharmaceuticalproductsin2005,BIappliedforapatentonthehemihydrateformofNVP,whichrelatestothepaediatricsuspension.CivilsocietygroupsinIndiafiledapre-grantoppositiontoBI’spatentapplicationinMay2006.InJune2008,thepatentapplicationontheNVPhemihydratewasrejectedbytheIndianpatentoffice,allowingforunrestrictedcompetitiononthepaediatricformulation.ThisconstitutedanimportantvictoryforIndiancivilsociety,asthiswasthefirstpatentapplicationrelatedtoaHIVmedicinetohavebeenrejectedasaresultofapre-grantoppositionprocess,inaccordancewiththe2005IndianPatentsAct.75

PaediatricsNVPisapprovedforuseandiswidely-usedinchildren.

WiththeincreasedprevalenceofTB/HIVco-infection,thereisaneedforfurtherstudiesintotheinteractionsbetweenNVPandtheTBdrugsrifampicinandrifabutininchildren.29

BIhasaNVPdonationprogrammeforthepreventionofmother-to-childtransmission(PMTCT).This,however,doesnotcovertreatmentforchildren.WhenBIannouncedareductionof50%forNVPinmid2007,itdidnotincludetheNVP10mg/mlsolution,whereapricedropwouldhavehadaconsiderableimpact.Itthereforecostsmoretotreata10kgchildwithNVPthananadult.

Genericmanufacturershavebeendevelopingtriplefixed-dosecombinationsincludingNVP,buttodayonlythreepaediatrictripleFDCsthatincludeNVPareincludedintheWHOPrequalificationListofMedicinalProducts.

AnewformulationofNVP20mgscoredtabletissuggestedbytheWHOPaediatricAntiretroviralWorkingGroupforthenewWHOPMTCTguidelinesforinfantprophylaxis.137

Nevirapine ( NVP ) continued


ABACAVIR ( ABC )A

BA

CA

VIR

( AB

C )

NU

CL

EO

SID

E &

NU

CL

EO

TID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

INH

IBIT

OR

S ( N

RT

I & N

tRT

I )

GENERAL INFORMATION

•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).

•Indicatedforfirst-andsecond-line:foradults,adolescentsandchildren.8,137

•Originatorcompany,andproductbrandname:GlaxoSmithKline(GSK),Ziagen.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.


AsofApril2010,therewerefourgenericsourcesofABC300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Since2001,theoriginatorpricehasdecreasedby68%,whilethegenericpricehasdecreasedby92%.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):December1998.17


•Worldsalesoforiginatorproductfor2009:US$160million;2008:$175million;2007:$215million;2006:$230million;2005:$268million;2004:$290million.77,78,79,80,81,82

•ThebasicpatentsonABCwereappliedforbyGSKin198983and1990,83andtheseareduetoexpirein2009and2010,respectively.GSKsubsequentlyappliedforanadditionalpatentsrelatedtonewintermediatesin1995,84toonthehemisulfatesaltofABCin199885andtocompositionsofABCparticularlyrelevantforpaediatricusein1999,which 86areduetoexpirein2015,2018and2019,respectively.

Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

3000

2500

2000

1500

1000

500

0


generic priceABC 300mg tablet

438

207

1387

2628

Continued overleaf

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides



ABC20mg/mloralsolution

10ml 230 (0.063/ml)

212 (0.058/ml)

113 (0.031/ml)

ABC60mgtablet 4 153 (0.105)

134(0.092)

183 (0.125)

540(0.370)

ABC300mgtablet 2 438 (0.600)

243 (0.333)

207 (0.283)

256(0.350)

219 (0.300)

274 (0.375)



AB

AC

AV

IR (

AB

C )

NU

CL

EO

SID

E &

NU

CL

EO

TID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

IN

HIB

ITO

RS (

NR

TI

& N

tRT

I )


InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Forsecond-linetreatment,proteaseinhibitorssuchasritonavir-boostedatazanavir(ATV/r)orlopinavir(LPV/r),andsimplifiedNRTIoptionsarerecommended.Abacavir(ABC)anddidanosine(ddI)arenolongerrecommendedasoneoftheNRTIbackbonesinsecond-linetherapy.9

EventhoughthepriceofABChasfallenbyalmost92%ingenericpricingsince2001,thecurrentlowestgenericpriceismorethantwicethelowestpriceoftenofovir(TDF)orzidovudine(AZT).Additionally,GSK’sdifferentialpricingstructure(seeannex2)excludessomelow-andmiddle-incomecountriesthatarenotfundedbytheGlobalFund.Thecurrentpriceinthedevelopedworldof$4,600ppyisprohibitiveformanydevelopingcountriesthatneedtoaccesstheproduct.87

PatentsThepriceofABCdecreasedsignificantlywiththearrivalofgenericcompetition.SuchcompetitionwasmadepossiblebecauseGSKcouldnotapplyforthebasicpatentsonABCincountrieswithgenericproductioncapacitysuchasIndia,whichdidnotgrantpatentsonpharmaceuticalsatthetime.

However,patentshavebeengrantedinChina39,andGSKhasappliedforpatentsonthehemisulfatesaltofABCandoncompositionsofABCparticularlyrelevantforpaediatricuseinIndia.GSKwithdrewitspatentapplicationonthehemisulfatesaltofABCinOctober2007afteritwasopposedbycivilsocietygroupsinJuly2006inapre-grantoppositionprocedure.88Nevertheless,thepatentmorespecificallyrelatedtopaediatricformulationswasgrantedinDecember2007.89ThispatentraisesconcernsoverthecontinuedgenericavailabilityoftheABCpaediatricformulation,whichisanimportantoptionforyoungchildrenwithHIV/TBco-infection.

PaediatricsABCisapprovedforuseinchildren.

Thereisaliquidformulationandtoday,twogenericsourcesofpaediatricABC60mgtabletareincludedintheWHOListofPrequalifiedMedicinalProducts.

ABCwillcontinuetobeanimportantdrugforHIV/TBco-infectedsmallchildren,whohavelimitedchoicesofARVsbecauseofdruginteractionsbetweenTBdrugsandnevirapine(NVP),andbecauseofthelackofdosagedataonefavirenz(EFV)forchildrenunderthree.

Today,once-dailydosingofABCisonlyrecommendedforpatientsover12yearsofage;morestudiesareneededtoconfirmthesafetyofdailydosingofABCinchildren.90

Abacavir ( ABC ) continued


DIDANOSINE ( ddI )D

IDA

NO

SIN

E ( d

dI )

NU

CL

EO

SID

E &

NU

CL

EO

TID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

INH

IBIT

OR

S ( N

RT

I & N

tRT

I )

GENERAL INFORMATION


•Indicatedforsecond-lineforchildren.137

•Originatorcompanyandproductbrandname:Bristol-MyersSquibb(BMS),Videx/VidexEC.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):October1991forchewabletablets;October2000forenteric-coatedcapsules.17


•Worldsalesoforiginatorproduct:2005:US$174million;2004:$274million;2003:$354million.After2005,therearenosalesfigureslistedinthecompany’sannualreport.49

•ThebasicpatentonddIfiledin1985bytheNationalInstitutesofHealth(NIH),aU.S.governmentresearchinstitute,hasexpired,butBMSholdspatentsonimprovedformulationsinsomecountries,whichrununtil2012and2018.91

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/capsule/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

BMS

Aurobindo Cipla RanbaxyCategory1countries

Category2countries

Whocanaccessthisprice? Seeannex2&annex7 Norestrictions

ddl2gpowderforreconstitution(finalconcentration10mg/ml)

12ml 276 (12.590/2g)

308 (14.057/2g)

88 (4.000/2g)

ddl25mgtablet 5 212 (0.116)

429 (0.235)

115(0.063)

228(0.125)

ddl50mgtablet - (0.158) (0.235) (0.079) (0.115)

ddl100mgtablet 4 311 (0.213)

364 (0.249)

194 (0.133)

188(0.129)

242(0.166)

ddl125mgenteric-coatedcapsule 1 110 (0.300)

ddl150mgtablet - (0.308) (0.345) (0.225) (0.167)

ddl200mgtablet - (0.267) (0.257)

ddl200mgenteric-coatedcapsule - (0.383)


249 (0.683)

170 (0.467)

103(0.283)


322 (0.881)

256 (0.700)

132(0.363)

Continued overleaf


Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

US$

pp

y

Month/Year

350

300

250

200

150

100

50

0Jun10

268


generic priceddI EC 400mg capsule

288270271

DID

AN

OSIN

E (

dd

I )

NU

CL

EO

SID

E &

NU

CL

EO

TID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

IN

HIB

ITO

RS (

NR

TI

& N

tRT

I )


InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Forsecond-linetreatment,proteaseinhibitorssuchasritonavir-boostedatazanavir(ATV/r)orlopinavir(LPV/r),andsimplifiedNRTIoptionsarerecommended.Abacavir(ABC)anddidanosine(ddI)arenolongerrecommendedasoneoftheNRTIbackbonesinsecond-linetherapy.9

BMS’sdifferentialpricingstructurelimitsthepricesquotedabovetosub-SaharanAfricaandlow-incomecountries.ThisstructureleavessomecountriespayingmorethanUS$3,600perpatientperyearforddI400mgenteric-coated(EC)capsules,whichisprohibitiveformanyofthesecountries.87

In2007,BMSannounceditsplanstorestructurethecompanyintoaBioPharmacompany.Theplansincludereducingthenumberofbrandsinthecompany’smatureproductsportfolioby60%between2007and2011andreducingofthecompany’smanufacturingfacilitiesbymorethan50%bytheendof2010.92Asaresult,BMShas

takenadecisiontocloseitsmanufacturingplantinMeymac,France,inJune2010whichmightaffecttheavailabilityofsomeantiretroviralsforthedevelopingworlduntilthenewproductionplantintheU.S.isabletoproducethoseformulationsagain.In2006,BMSdiscontinuedthesaleofthechewable/dispersiblebufferedtabletsintheU.S.Theenteric-coatedcapsulesaremoreadaptableastheycanbetakenoncedailyand,unlikethetablets,donotcontainabuffer.Thebufferhasbeenassociatedwithstomachupsetsandabitterandchalkytaste.

InDecember2009,BMSdiscontinuedthesaleandmanufacturingofddI200mgtabletgloballyduetolowdemandfortheproduct.

Today,fourgenericddIECformulationsareincludedintheWHOListofPrequalifiedMedicinalProducts.

Patents

Thepatentonenteric-coatedcapsuleswasgrantedinBrazil,China,andARIPOandOAPIcountries.Noapplicationclaimingapatentonenteric-coated

capsuleshasbeenpublishedinIndia,allowingagenericversiontobelaunched.However,wherethepatenthasbeengrantedinotherdevelopingcountries,theimportationofthemoreaffordableversionfromIndiaisblocked.

Paediatrics

Foryoungerchildren,theonlyoptionsarebufferedtabletsthatcomewithahighpillburden,ortheddIpowderforreconstitution,whichrequiresmultipledilutions,firstwithwaterandthenwithanantacid,toobtainthefinalconcentration.Oncereconstituted,thesolutionmustberefrigeratedandmustbediscardedafter30days.

BMSoffersnodifferentialpricefortheddIEC125mg,whichisthebest-adaptedoptionforolderchildrenwhocanswallow.

DuetotheimminentclosureoftheBMSfacilityinMeymac,France,inJune2010,aserioussupplyproblemfordidanosine25mgand50mgtabletsofwhichthereisnoWHOprequalifiedgenericsource,islikelytoemerge.


AsofApril2010,therewasonegenericsourceofddI400mgenteric-coatedcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.

Didanosine ( ddI ) continued


EMTRICITABINE (FTC)E

MT

RIC

ITA

BIN

E ( F

TC

)N

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GENERAL INFORMATION


•Indicatedforfirst-andsecond-lineforadultsandadolescents.8

•Originatorcompanyandproductbrandname:Gilead,Emtriva.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):July2003.17


•Worldsalesoforiginatorproduct:2009:US$28million;2008:$31million;2007:$32million;2006:$36million;2005:$47million;2004:$58million.93,94,95,96

•ThebasicpatentonFTCandlamivudine(3TC)wasfiledbyIAFBiochemin1990andisduetoexpirein2010.AsthemolecularstructureofFTCand3TCareverycloselyrelated,thesamepatentcoversboththesedrugs.97,98

•EmoryUniversityalsoappliedforaseriesofpatentsthatrelatetoFTCbetween1990and1992.99,100Theseareduetoexpirebetween2010and2012.In2005,GileadacquiredtheroyaltyinterestforFTCundera$525millionagreementwithEmoryUniversity.101

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.


Emtricitabine(FTC)producedbyGileadisnotofferedaspartofthecompany’sAccessProgramandisalsoneitherregisterednormarketedindevelopingcountries.Itis,however,availableinco-formulationwithtenofovir(TDF)andefavirenz(EFV).

AccordingtotheWHOtreatmentguidelines,‘FTCisanequivalentalternativetolamivudine(3TC)asitisstructurallyrelatedto3TC,sharesthesameefficacyagainstHIVandhepatitisBvirus(HBV)andhasthesameresistanceprofile.’8

ThenewWHO2010guidelinesrecommendusingTDFwitheitherFTC-or3TC-containingantiretroviralregimensinallHIV/HBVco-infectedindividualsneedingtreatment.9

PatentsAlthoughbasicpatentsonFTCcouldnotbeappliedforinIndiabecausethecountrydidnotgrantpatentsonpharmaceuticalsatthetime,GileadreportedholdingpatentrightsonFTCin45otherdevelopingcountries.102

Inmid2006,Gileadsignedlicensingagreementswith10genericmanufacturersinIndia,allowingthemtomanufactureandexportgenericversionsofGilead’sTDFincombinationwithotherARVs–includingFTC–toalimitedlistofcountries,inreturnforthepaymentofa5%royalty.103

PaediatricsFTCisapprovedforuseinchildrenandhastheadvantageofonce-dailydosing.

ThepaediatricformulationproducedbyGileadisasolutionthatrequiresrefrigerationpriortodispensingandmustbeusedwithinthreemonthsandstoredattemperaturesbelow25°C.Thisisnotadaptedtodevelopingworldneeds.

Dailydose Aurobindo Matrix

Whocanaccessthisprice? Norestrictions

FTC200mgcapsule 1 63 (0.173)

79 (0.217)


GENERAL INFORMATION



•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Epivir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

LAMIVUDINE ( �TC )L

AM

IVU

DIN

E (

�T

C )

NU

CL

EO

SID

E &

NU

CL

EO

TID

E R

EV

ER

SE

TR

AN

SC

RIP

TA

SE

IN

HIB

ITO

RS (

NR

TI

& N

tRT

I )

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):November1995.17


•Worldsalesoforiginatorproduct:2009:US$197million;2008:$225million;2007:$309million;2006:$398million;2005:$398million;2004:$549million.104,80,81,82

•Thebasicpatentonemtricitabine(FTC)and3TCwasfiledbyIAFBiochemin1990andisduetoexpirein2010.AsthemolecularstructureofFTCand3TCareverycloselyrelated,thesamepatentcoversboththesedrugs.97

•GSKobtainedalicensefromIAFtomanufacture3TCandfiledadditionalpatentsonnewformsof3TCin1992,whichareduetoexpirearound2012.105

•GSKalsoappliedforanewformulationpatentin1998.ThispatentwasgrantedinBrazil,ChinaandinARIPOcountries.106

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix Ranbaxy(CF) Strides

Whocanaccessthisprice? Seeannex2 Norestrictions

3TC10mg/mloralsolution

10ml 84 (0.023/ml)

29 (0.008/ml)

37 (0.010/ml)

37(0.010/ml)

3TC150mgtablet 2 64 (0.087)

34 (0.047)

35 (0.048)

33 (0.045)

34 (0.046)

34 (0.047)

37 (0.050)

3TC300mgtablet 1 24 (0.067)

41(0.113)

38 (0.103)

34 (0.092)


AsofApril2010,therewereninegenericsourcesof3TC150mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Thepriceoftheoriginatorproducthasfallenby73%since2001,whilegenericpriceshavedroppedby64%.

Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

US$

pp

y

Month/Year

250

200

150

100

50

0Jun10


generic price3TC 150mg tablet

91

33

64

234

(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.



Lamivudine(3TC)isawidely-usedARVbothinfirst-andsecond-lineregimens.Ithasbeenanimportantcomponentoffixed-dosecombinationsthathavefosteredtreatmentscale-upinresource-limitedsettings.

AccordingtotheWHOtreatmentguidelines,‘FTCisanequivalentalternativetolamivudine(3TC)asitisstructurallyrelatedto3TC,sharesthesameefficacyagainstHIVandhepatitisBvirus(HBV)andhasthesameresistanceprofile.’8

ThenewWHO2010guidelinesrecommendusingTDFwitheitheremtricitabineor3TC-containingantiretroviralregimensinallHIV/HBVco-infectedindividualsneedingtreatment.9

LA

MIV

UD

INE

( �T

C )

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AN

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I )

PatentsAsthegraphillustrates,thepriceof3TCdecreaseddramaticallyaftertheonsetofgenericcompetition.Genericcompetitionfor3TCoriginatedincountrieswithmanufacturingcapacitywherethedrugisnotunderpatent,suchasIndia,ThailandandBrazil.

InChina,whereGSKstillownsexclusiverightson3TC,thepriceofthemedicineremainsveryhigh,ataroundUS$1,780perpatientperyear.GSKisusingitsmonopolyrightstoblocklocalproductionorimportationofmoreaffordablegenericversionsof3TC.

Paediatrics

3TCisapprovedforuseandiswidelyusedinchildren.

Genericmanufacturershavebeendevelopingbothdoubleandtriplefixed-dosecombinationscontaining3TC.AsofApril2010therewerefourpaediatrictripleFDCscontaining3TCincludedintheWHOListofPrequalifiedMedicinalProducts.

Today,once-dailydosingof3TCisonlyrecommendedforpatientsover16;morestudiesareneededtoconfirmthesafetyofdailydosingof3TCinchildren.90


GENERAL INFORMATION


•Indicatedforfirst-lineforchildrenandalsorecommendedtomoveawayfromd4Tfirst-lineinadultsandadolescents.8,137

•WHOupdatedthe2006guidelinestorecommendareductionindoseofd4T40mgtod4T30mgforallweightcategoriesofpatients.107

•Originatorcompanyandproductbrandname:Bristol-MyersSquibb(BMS),Zerit.


STAVUDINE ( d�T ) ST

AV

UD

INE

( d

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UC

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TA

SE

IN

HIB

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NR

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•Includedinthe16theditionWHOModelListofEssentialMedicines(EML).26

•Worldsalesoforiginatorproduct:2006:US$155million;2005:$216million;2004:$272million;2003:$354million.After2006,therearenosalesfigureslistedinthecompany’sannualreport.108,49

•d4TwastheresultofU.S.publicsectorresearch.ItwasoriginallysynthesisedbytheMichiganCancerFoundationin1966underagrantfromtheNationalCancerInstitute.109ResearchersfromYaleUniversitythendiscovereditsantiretroviralactivityandappliedforapatent

inDecember1987,mostlyindevelopedcountries,fortheuseofd4Ttotreatpatientsinfectedwithretroviruses.110ThispatentshouldhaveexpiredinDecember2007,buttheprotectionwasextendeduntiltheendof2008intheU.S.anduntil2011inmostEuropeancountries.BMSmarketsd4TunderamarketinganddistributionlicencefromYaleUniversity.

•Patentshaveexpiredinmostothercountriesatthispoint.

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/doseofpowderfororalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

BMS

Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy(CF) StridesCategory1countries

Category2countries



d4T1mg/mlpowderfororalsolution

20ml 51 (0.007/ml)

58 (0.008/ml)

58 (0.008/ml)

44 (0.006/ml)

d4T15mgcapsule

- (0.082) (0.093) (0.026) (0.024) (0.025)

d4T20mgcapsule

- (0.089) (0.093) (0.027) (0.025) (0.028)

d4T30mgcapsule

2 48 (0.066)

68 (0.093)

20 (0.028)

26(0.035)

21 (0.029)

24 (0.033)

26 (0.035)

22 (0.030)



ST

AV

UD

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( d�

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NU

CL

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SID

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NU

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SE

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SE

INH

IBIT

OR

S ( N

RT

I & N

tRT

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Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationand,mostimportantly,itslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.

InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9

PatentsYaleUniversitydidnotapplyforpatentsinmostdevelopingcountriesexceptforSouthAfrica.Therefore,genericmanufacturersfromcountrieswithmanufacturingcapacity,suchasBrazil,China,IndiaorThailandcouldlegallymanufactureandexportaffordablegenericversionsofd4T.

InSouthAfrica,whereBMSmarketedd4TunderanexclusivelicensefromYale,thedrugwas34timesmoreexpensivethangenericversionsavailableinothercountries.ThispromptedapatentcontroversyinMarch2001,particularlyasthemedicinehadbeendevelopedwithpublicfunds.Afterpressurefromresearchers,students,andaccessadvocates,YalerenegotiateditslicensewithBMStoallowtheimportationofmoreaffordablegenericversionsofd4TtoSouthAfrica.109

PaediatricsStavudineisapprovedforuseinchildren.

Thepaediatricformulationofd4Tisnotadaptedforresource-limitedsettingsasitissuppliedasapowderthatrequiresreconstitutionwithclean,safewater,andoncereconstituted,mustberefrigerated.

Genericmanufacturershavebeendevelopingbothdoubleandtriplefixed-dosecombinationsincludingd4T.Forpaediatricuse,twod4t-containingtripleFDCsareincludedinWHOListofPrequalifiedMedicinalProducts.

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

US$

pp

y

Month/Year

60

50

40

30

20

10

0Jun10


generic priced4T 30mg capsule

20

36

49 48


AsofApril2010,thereweresixgenericsourcesofd4T30mgcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.


GENERAL INFORMATION

•Therapeuticclass:nucleotidereversetranscriptaseinhibitor(NtRTI).


•Originatorcompanyandproductbrandname:Gilead,Viread.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):October2001.17


AsofApril2010,therewerefourgenericsourcesofTDF300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Therehasbeena77%decreaseinthegenericpricesince2006,anda56%decreaseinthelowestoriginatorpricesince2003.

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

500

450

400

350

300

250

200

150

100

50

0


generic priceTDF 300mg tablet

85

365

475

204

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.


•Worldsalesoforiginatorproduct:2009:US$667million;2008:$621million;2007:$613million;2006:$689million;2005:$778million;2004:$783million.93,94,111,112,95,96

•ThebasicpatentontenofovirwasappliedforbytheAcademyofSciencesoftheformerCzechoslovakiain1986.Ithasnowexpiredinmostcountries.113

Gileadsubsequentlyappliedforadditionalpatentsrelatedtotenofovirdisoproxilin1997 114andtothefumaratesaltoftenofovirdisoproxilin1998.115Theseareduetoexpirein2017and2018,respectively.Inaddition,GileadandBMShaveappliedforpatentsonfixed-dosecombinationsofTDF/FTCandTDF/FTC/EFVwhich,ifgrantedindevelopingcountries,willnotexpirebefore2024and2026respectively.58,59

TENOFOVIR DISOPROxIL FUMARATE ( TDF )

TE

NO

FO

VIR

DIS

OP

RO

xIL

FU

MA

RA

TE

( T

DF )

NU

CLEO

SID

E &

NU

CLEO

TID

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SE T

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NH

IBIT

OR

S (

NR

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& N

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��

Dailydose

Gilead

Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy StridesCategory1countries

Category2countries



TDF300mgtablet 1 204 (0.559)

360 (0.986)

100 (0.275)

87 (0.237)

103(0.283)

85 (0.233)

152 (0.417)

146(0.400)


Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org


InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.

Formanyyears,astavudine-based(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationand,mostimportantly,itslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.

Itistime,however,forcountriestoinvestinamorerobust,TDF-containingfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepill,onceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9

Forsecond-linetreatment,TDFincombinationwithlamivudine(3TC)oremtricitabine(FTC)aretherecommendedNRTIbackbonestobeaddedtoaboostedproteaseinhibitor,ifstavudineorzidovudinehavebeenusedinthefirst-lineregimen.

TDFisalsoactiveagainsttheHepatitisBvirus(HBV)andthereforeplaysanimportantroleinco-infectedpatients.ForHIVpatientsrequiringtreatmentforHBV,thetreatmentshouldcontainTDFandeither3TCorFTC.

Gileadhasadifferentialpricingstructure(seeannex9)thathasbeenexpandedtoincludelower-middle-incomecountriesnotincludedinitsAccessProgram.

PatentsGileadhasappliedforpatentsrelatedtoTDFinmanydevelopingcountries,includingIndia,BrazilandChina.InBrazilandIndia,thesepatent

TE

NO

FO

VIR

DIS

OP

RO

xIL

FU

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( TD

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NU

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NU

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��

applicationshavebeenopposedbycivilsocietygroups,aswellasbysomegenericmanufacturers.

Inamajorvictoryforaccesstomedicines,theIndianpatentofficerejectedseveralpatentapplicationsrelatingtoTDFinSeptember2009.Thepatentswererejectedonthegroundsthattheylackaninventivestep–theydonotmeettherequirementofenhancedefficacystipulatedunderSection3(d)ofIndia’spatentlaw.Further,combinationsofknownmoleculesarenotpatentableunderIndianpatentlaw.174,175,176

Nevertheless,divisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)havebeenfiledbyGileadforthisandotherpatentapplications.Thismeansthatalthoughthepatentwasnotgranted,thepatentapplicationsarestillpendingbeforethepatentoffice.116,117

ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI–Brazilianpatentoffice)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasrequestedadivisionalpatent,whichhasbeenopposedbycivilsocietygroups.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.

Followingoppositions(bymembersofIndianandBraziliancivilsociety)tothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandoneinSouthAfrica,allowingthemtomanufactureandexportgenericversionsofTDFandTDF-basedFDCstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103

Manufacturersthathavesignedtheseagreementsareunabletosupply

countriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,BrazilistodaypayingUS$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129TheBraziliangovernmentiscurrentlysupportingthedevelopmentofgenericTDFthroughpartnershipsbetweenBrazilianpublicandprivatemanufactures.

AlthoughthelicensingagreementssignedbyGileadcancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,theyshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.

PaediatricsInMarch2010,TDFwasapprovedbytheU.S.FDAforuseinadolescentsolderthan12yearsoldandweighingmorethan35kg.118

Gilead’sPhaseIItrialinvolvingchildren(agedbetweentwoand12years),usinganoralpowderformulationisstillon-going.Suchdata,providedappropriateformulationsaredeveloped,willbecrucialtoaddresstheurgentneedsofthispaediatricpopulation.

InMarch2009,U.S.FDAgrantedTDFanOrphanDrugdesignationfortreatmentofpaediatricHIVinfections.119Gileadisnowentitledtosevenyearsofmarketingexclusivityforthedesignatedpaediatricindication,taxcreditsforclinicalresearchandcanapplyforgrantstodefraythecostofclinicaltrials.120


ZIDOVUDINE ( AZT or ZDV )

GENERAL INFORMATION



•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Retrovir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):March1987.17


•Worldsalesoforiginatorproduct:2005:US$84million;2004:$80million.After2005,therearenosalesfiguresforthisproductlistedinthecompany’sannualreport.78,79

•AZTwasfirstdiscoveredin1964asananti-cancermedicine.TheU.S.NationalInstitutesofHealthdidthemajorityoftheresearchthatshowedthedrug’seffectivenessasanantiretroviral.GlaxoWellcomefiledforpatentsonAZTforthetreatmentofAIDSandbroughtthedrugontothemarketin1987asoneofthemostexpensiveeversold.Patentshaveexpiredinmostcountriesatthispoint.

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/capsule/doseofsuspension.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

ZID

OV

UD

INE

( A

ZT

or

ZD

V )

NU

CL

EO

SID

E &

NU

CL

EO

TID

E R

EV

ER

SE

TR

AN

SC

RIP

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SE

IN

HIB

ITO

RS (

NR

TI

& N

tRT

I )

Dailydose

ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy(CF)


AZT10mg/mlsuspension 20ml 234 (0.032/ml)

66 (0.009/ml)

80 (0.011/ml)

66(0.009/ml)

AZT60mgtablet 4 115 (0.079)

AZT100mgcapsule - (0.122) (0.051) (0.050)

AZT250mgcapsule - (0.276)

AZT300mgtablet 2 161 (0.221)

101 (0.138)

97 (0.133)

100 (0.137)

91 (0.125)

91 (0.125)





InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-term

irreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9

Forsecond-linetreatment,andiftenofovirhasbeenusedinthefirst-line,AZTincombinationwithlamivudine(3TC)istherecommendedNRTIbackbone,towhichaboostedproteaseinhibitor(PI)shouldbeadded.

Patents

Patentshaveexpiredinmostcountriesatthispoint.

Paediatrics

AZTisapprovedforuseandiswidelyusedinchildren.

Genericmanufacturershavebeendevelopingbothdoubleandtriplepaediatricfixed-dosecombinationsincludingAZT.Today,however,therearefourpaediatricFDCs

containingAZTthatareincluded

inWHOListofPrequalified

MedicinalProducts.

Todaythereisonegenericversion

ofAZT60mgwhichisprequalified

byWHO.

Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

800

700

600

500

400

300

200

100

0


generic priceAZT 300mg tablet

684

161

91

193


AsofApril2010,thereweresevengenericsourcesofAZT300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Since2001,theoriginatorpricehasdecreasedby76%,whilethegenericpricehasdecreasedby53%.

ZID

OV

UD

INE

( AZT

or Z

DV

)N

UC

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OSID

E &

NU

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EV

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TR

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RIP

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INH

IBIT

OR

S ( N

RT

I & N

tRT

I )


GENERAL INFORMATION

•Therapeuticclass:proteaseinhibitor(PI).

•BoostedATVisindicatedforsecond-lineforadultsandadolescents.8

•Originatorcompanyandproductbrandname:Bristol-MyersSquibb(BMS),Reyataz.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):June2003.17

ATAZANAVIR ( ATV )



Medicines(EML).26

•Worldsalesoforiginatorproduct:2009:

US$1.4billion;2008:$1.3billion;

2007:$1.1billion;2006:$931million;

2005:$696million;2004:$369million;

2003:$81million.121,50,122,108,123

•ThebasicpatentwasfiledinApril1997byNovartisandisexpectedtoexpireinApril2017.124Bristol-MyersSquibbismanufacturingATVunderlicencefromNovartis.BMSalsoappliedforpatentsonthecrystallinebisulfatesaltofATVinDecember1998125andonaprocessforpreparingthebisulfatesaltandnovelformsin2005.126


Dailydose

BMS

Matrix(CF)Category1countries

Category2countries


ATV150mgcapsule 2* 353 (0.484)

431 (0.590)

ATV200mgcapsule - (0.602) (0.743)

ATV300mgcapsule 1*256(0.700)

AT

AZ

AN

AV

IR (

AT

V )

PR

OT

EA

SE

IN

HIB

ITO

RS (

PI )

*ThedoseofATVmustbeboostedwithRTV100mgonceaday.



AT

AZ

AN

AV

IR ( A

TV

)P

RO

TE

ASE

INH

IBIT

OR

S ( P

I )


InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).9Withitsonce-a-daydosingATVisthemostpatient-friendlyPIofthetwo.

ATV,likeallPIs(withtheexceptionofnelfinavir(NFV),requiresboostingwithRTV.Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.

TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingATV.

AsATVisoneofthetwoPIsrecommendedbyWHO,thereisanurgentneedforgenericmanufacturerstosupplyaheat-stableATV/rfixed-dosecombination.Currentlythisfixed-dosecombinationisnotproducedbytheoriginatorcompanies.

PatentsPatentapplicationsrelatedtoATVhavebeenfiledbyNovartisandBMSinmostdevelopingcountrieswithgenericpharmaceuticalproductioncapacity,includingBrazil,China

andIndia.MostpatentshavebeengrantedinBrazilandChina.InIndia,wherethepatentapplicationsarestillunderexamination,civilsocietyorganisationsfiledapre-grantoppositiontoNovartis’sbasicpatentapplicationonthegroundsoflackofnovelty,127buttheotherpatentapplicationswarrantadditionalpre-grantoppositions.

Inaddition,AbbotthasfiledpatentapplicationsonRTVinIndiaandotherdevelopingcountries,which,ifgranted,willblockthedevelopmentofandaccesstogenericATV/rfixed-dosecombinations.

BMSinFebruary2006grantedtechnologytransferandvoluntarylicencestotwogenericmanufacturers(EmcureandAspen)tomanufactureandsellATV.InFebruary2008,EmcurereceivedU.S.FDAtentativeapprovalforthe100mg,150mgand200mgATVcapsules.Underthetermsofthelicenses,however,salesoftheseproductsareroyalty-freebutarerestrictedtosub-SaharanAfrica.

BMShasaseparateagreementwithEmcurethatcoversIndia.128

LicensingagreementsinIndiashouldnotbenecessaryifpatentoppositionsaresuccessful.Ifpatentsaregranted,Indiaandothercountriescouldissuecompulsorylicencestoenableunrestrictedcompetitionfrom

genericmanufacturers,inordertobringpricesdown,increaseaccessandfacilitatethedevelopmentofanATV/rfixed-dosecombination.

BMS’sdifferentialpricingstructureislimitedtosub-SaharanAfricaandlow-incomecountries.Thisstructureleavesmiddle-incomecountriessuchasBrazilpayingmorethanUS$1,400perpatientperyear,whichisprohibitiveformanyofthesecountries.129

Paediatrics

InMarch2008,ATVwasapprovedforuseinchildrenbetween6and18yearsofage.17

In2008,WHOrecommendedearlytreatmentforallHIV-positivechildren,andchildrenwhohavebeenexposedtonevirapineeitherthroughtheirmotherorthroughasingledoseinapreventionofmother-to-childtransmission(PMTCT)programme.WHOrecommendsthesechildrenshouldbestartedonaPI-basedregimen.130Today,theonlyoptionforthesechildrenistheLPV/rformulation.

Tosimplifytreatmentforallchildren,thereisanurgentneedforstudiesonATVtobecompleteddowntoinfants,andchild-adaptedformulationstobemadeavailable.


GENERAL INFORMATION


•BoostedDVRislistedinWHOguidelineasapotentialthird-linedrug.8

•Indicatedfortreatment-experiencedpatients,suchasthosewithHIV-1strainsresistanttomorethanoneproteaseinhibitor(adults).Itisalsoindicatedindevelopedcountriesfortreatment-naivepatients.131

DARUNAVIR ( DRV )

•Originatorcompanyandproductbrandname:Tibotec(adivisionofJohnson&Johnson),Prezista.

•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):June2006.17

•Worldsalesoforiginatorproduct:therearenosalesfigureslistedinthecompany’sannualreport.

•Notincludedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26

•ThebasicpatentwasappliedforbySearleandMonsantoinAugust1993,132andisduetoexpirein2013.Subsequently,NIHandtheUniversityofIllinoisappliedforpatentsmorespecificallyrelatedtodarunavirin1999133andlicensedthemtoTibotecfordevelopment.134Tiboteclaterappliedforpatentsrelatedtoimprovedformsandcombinationsofdarunavir.


DA

RU

NA

VIR

( D

RV

)P

RO

TE

ASE

IN

HIB

ITO

RS (

PI )

Dailydose Tibotec


DRV300mgtablet 4*1095(0.750)

*ThedoseofDRVmustbeboostedwithRTV100mgtwiceaday.



InDecember2009,WHOreleasednewrecommendationswhichforthefirsttimecallfortheneedofthird-linetherapy.Asmanystudiesareongoing,drugslikelytohaveanti-HIVactivityinthird-lineregimensareboosteddarunavir,etravirineandraltegravir.9

Tibotecsignedaroyalty-free,non-exclusivelicenseagreementwithAspenofSouthAfricaon4April2007.ThisgrantsAspentherighttoregister,packageanddistributedarunavir(DRV)insub-SaharanAfrica.InDecember2008,Tibotecannouncedthesigningofaroyalty-free,non-exclusivelicenseagreementwithEmcuretodistributeDRVinIndia.136Theseagreementsexcludeotherlow-andmiddle-incomecountries,forwhichthepricepaidinwealthycountries,atoverUS$11,400perpatientperyear,isprohibitive.37

Morerecently,Tiboteccompletedasupplyandco-marketingagreementwithAspenPharmacarecoveringallofAfrica.Underthisagreement,Aspenwillhandleregulatory,registration,anddistributionactivities.Atthetimeofwriting,theAspen/Tibotecproductisregisteredinatleasteightcountrieswithapplicationsinprocessin11others,primarilyforthe400mgproductbutalsofor300mgandpaediatricformulations.PatientnumbersinAfricaforDRVarestillsmall,andAspenhasagreedtoa$1,095perpatientperyearfor300mgand400mgformulations.

InBrazil,DRVwasincludedinthegovernment’sguidelinesin2008,

butat$6,037perpatientperyear(boostedwithritonavir),itisveryexpensive.129

DRV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.

TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingDRV.

Thereisaneedforgenericmanufacturerstosupplyaheat-stableDRV/rfixed-dosecombination.Currentlythisfixed-dosecombinationisnotproducedbytheoriginatorcompanies.

PatentsEventhoughbasicpatentsrelatedtoDRVcouldnotbeappliedforinIndiabefore1995,TibotechasappliedforseveralpatentsinIndiarelatedtonewformsandcombinationsofDRVwithtenofovir(TDF)andritonavir(RTV),someofwhichhavebeenopposedbygenericmanufacturers.MostofthesepatentapplicationsremainunderreviewattheIndianpatentoffice.TheIndianpatentofficerecentlyrejectedtheDRVpatentrelatedtopseudopolymorph(whichwouldhavebeenduetoexpirein2023).AvoluntarylicensefortheDRVpseudopolymorphhasbeengrantedinSouthAfrica.

InChina,patentsrelatedtoracemicandpseudopolymorphicformsofDRV,methodsforpreparing

intermediatecompoundsofDRVanduseofDRVincombinationwithotherARVs,havebeengrantedtoTibotec.39

Similarly,manypatentshavebeenfiledinBrazil,suchasthoserelatedtothecombinationofDRVwithTDFandRTV,aswellasthoserelatedtothepreparationofkeyintermediatesandthepseudopolymorphicform.

PaediatricsInDecember2008,DRVwasapprovedforuseinchildrenbetweensixand18yearsofage.17

Apaediatric75mgtabletisavailable,butTibotechasnotprovidedpriceinformationforthisproduct.Itishowever,availableonacompassionateusebasis(freeofcharge)forsub-SaharanAfricaandleast-developedcountries,untilapre-approvalaccessprogrammeisestablishedwithalocalpartner.

ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofafixed-dosecombinationcontainingdarunavirandritonavirtobeahighpriority,thoughitisstillunclearwhattheratiooftheco-formulationwillbe.137

DA

RU

NA

VIR

( DR

V )

PR

OT

EA

SE

INH

IBIT

OR

S ( P

I )


PR

OT

EA

SE

IN

HIB

ITO

RS (

PI )

FO

SA

MP

RE

NA

VIR

( F

PV

or

f-A

PV

)

GENERAL INFORMATION



•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK)andVertexPharmaceuticals,Lexiva.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

FOSAMPRENAVIR ( FPV or f-APV )


InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).9Asfosemprenavir(FPV)wasnotidentifiedasoneofthepriorityproducts,itsusewillbelimitedinthedevelopingworld.9

WhileFPV/rbasedregimensshowgoodantiviralefficacyandaregenerallywelltoleratedintherapy-naïvepatients,theexperienceofthisdrugindevelopedcountriesislimitedandlittlecomparativedataisavailableintreatment-experiencedpatients.141

FPV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).

Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.

TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingFPV.

Patents

Patentapplicationshavebeenfiledforinmanydevelopingcountries.InBrazilthebasicpatentwasrejectedbythepatentoffice,althoughinDecember2009thecompanyfiledanappealagainstthedecision.

InChina,SouthAfrica,ARIPOandOAPIcountries,142mostpatentshavebeengranted.

InIndia,patentapplicationsontheFPVsalts,includingcalcium,havebeenfiledandarependingreviewbythepatentoffice.

Therearenogenericformulationsofthisproductavailabletoday.

Paediatrics

FPVwasapprovedforuseinchildrenabovetheageoftwoinOctober200717andapaediatricsuspensionisavailable.

•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA)on:October2003.17



•ThebasicpatentwasappliedforbyVertexPharmaceuticalsinMarch1998,138andduetoexpirein2018.Fosamprenavir,aphosphateesterprodrugofamprenavir,139wasdevelopedandlaunchedbyGSK,underlicensefromVertex.GSKalsoholdspatentsrelatedtoacrystallineformofthecalciumsaltofFPV,140duetoexpirein2019.

��

PRICE INFORMATION

Dailydose ViiV


FPV50mg/mlsuspension 12ml*648(0.148/ml)

FPV700mgtablet 2*1222(1.674)

*ThedoseofFPVmustbeboostedwithRTV100mgtwiceadayforadults.

Developing country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/doseoforalsuspension.


IND

INA

VIR

( IDV

)P

RO

TE

ASE

INH

IBIT

OR

S ( P

I )

��

INDINAVIR ( IDV )

GENERAL INFORMATION



•Originatorcompanyandproductbrandname:Merck,Crixivan.

•FirstapprovalbyU.S.FoodandDrug

Administration(FDA):March1996.17



Medicines(EML).26


•ThebasicpatentwasfiledforbyMerckin1991andisduetoexpirein2012incountriesgranting20-yearpatents.143


Dailydose

Merck

Aurobindo Cipla HeteroCategory1countries

Category2countries


IDV400mgcapsule 4* 394 (0.270)

686 (0.470)

292(0.200)

422(0.289)

390 (0.267)


AsofApril2010,thereweretwogenericsourcesofIDV400mgcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.


InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).AsIDVwasnotidentifiedasoneofthepriorityproducts,itsusewillbelimitedinthedevelopingworld.9

Themainconcernwasthatatastandarddoseof800mgwith100mgritonavir(RTV)twiceaday,IDVislesswelltoleratedthanotherPIs,particularlyinhotclimates.141Therehavebeensomesmallstudiesto

supportalowerdoseofIDV+RTV400+100mgtwiceadaywiththeaimtoreducetoxicity.TheU.S.FDAhasalsoapprovedtheuseofIDVat800mgeveryeighthourswithoutRTV.

IDV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithRTV.Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.

TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingIDV.

SomegenericmanufacturershavestoppedproductionofIDV,oronlymanufactureitforspecificorders,becauseofadecreaseindemandforthisproduct.

PatentsInBrazil,indinavirisoneoftheARVsproducedlocally.Thepatentapplicationwasfiledin1994,atatimewhenthecountrydidnotgrantpatentsonpharmaceuticals.Forthisreason,itwasrejected.

PaediatricsTheoptimaldosingregimenfortheuseofIDVinpaediatricpatientshasnotbeenestablishedandnopaediatricformulationexists.144

Oct 01

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1000

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600

400

200

0


generic priceIDV 400mg capsule

390394

876

600

*ThedoseofIDVmustbeboostedwithRTV100mgtwiceaday.


LO

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LOPINAVIR/ RITONAVIR ( LPV/r )

��

GENERAL INFORMATION

•Therapeuticclass:boostedProtease

Inhibitor(PI)inadoublefixed-dose

combination.

•Indicatedforsecond-line,foradults,

adolescentsandchildren.8,137

•FirstapprovalbyU.S.FoodandDrug

Administration(FDA):September2000

(soft-gelcapsules);October2005

(heat-stabletablets).17

Evolution of the lowest quoted price for developing countries since �00�:

AsofApril2010,therewasnogenericsourceofLPV/r133/33mgsoft-gelcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts,sothelowestpricedgenericisconsideredinthisgraph.TherewerehowevertwogenericsourcesofLPV/r200/50mgheat-stabletabletincludedinthelist.Theonewiththelowestpriceisshownhere.

ThegenericpriceofLPV/r200/50mgheat-stabletablethasdecreasedby54%since2007.

Dec 02

Jun02

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US$

pp

y

Month/Year

lowest originator price (200/50mg heat-stable)

generic price (133/33mg soft-gel)

4000

1000

800

600

400

200

lowest originator price (133/33mg soft-gel)

generic price (200/50mg heat-stable)

1034

LPV/r

3833

500 500

609

440

500

475

•Originatorcompanyandproductbrandname:AbbottLaboratories,Kaletra/Aluvia.


•Worldsalesoforiginatorproduct:2009:US$1.366billion;2008:$1.47billion;2007:$1.32billion;2004:$897million;2003:$754million;2002:$551million;2001:$292million.145,146,147

•Mostpatentsrelatedtoritonavir(RTV)alsocoverLPV/r.ThebasicpatentrelatedtoLPVwasappliedforbyAbbottin1996.148

•Inaddition,AbbottappliedforpatentsmorespecificallyrelatedtoLPV/rsoft-gelcapsulesin1997149whichareduetoexpirein2017.Anapplicationforapatentontheheat-stabletabletformulationwasalsofiledin2004,150which,ifgranted,wouldrununtil2024.

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/tablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

Abbott

Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF)Category1countries

Category2countries


LPV/r80/20mg/mloralsolution 4ml 176 (0.121/ml)

400 (0.274/ml)

LPV/r100/25mgheat-stabletablet 3 165 (0.151)

376 (0.343)

219 (0.200)

228 (0.208)

LPV/r133/33mgsoft-gelcapsule 6 500 (0.228)

1000 (0.457)

609(0.278)

LPV/r200/50mgheat-stabletablet 4 440 (0.301)

1000 (0.685)

475 (0.325)

463(0.317)

493(0.338)

486 (0.333)



LO

PIN

AV

IR/R

ITO

NA

VIR

( LP

V/r )

PR

OT

EA

SE

INH

IBIT

OR

S ( P

I )


InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).9

Theheat-stableformulationofLPV/rmanufacturedbyAbbottandIndiangenericcompaniesisnowmarketedindevelopingcountries.Incomparisontotheolder,soft-gelcapsuleformulation,thenewformulationhasalowerpillcount(reducingtheburdenfromsixtofourpillsperday),thereisnoneedforrefrigeration,andtherearenodietaryrestrictions.Itisnowapprovedasonce-a-daydosingintreatment-experiencedpatientswithfewerthanthreelopinavirresistance-associatedmutations.17Thisshouldenhanceadherence.However,pillburdenremainsanissue.

Theentryofgenericmanufacturersishavingapositiveeffectonthemarket,andpricesaredeclining.TheClintonFoundation’smostrecentannouncementhassomegenericmanufacturersofferingpricesofUS$440perpatiantperyear(seeannex13fordetails).

PatentsInIndia,Abbotthasappliedforseveralpatentsonthesoliddosageformulationandpolymorphicformsoflopinavir(LPV),ritonavir(RTV)andontheheat-stablecombinationofLPV/r,anumberofwhichhavebeenopposedbycivilsocietyorganisations151andgenericcompanies.Followingapre-grantoppositiontotheapplicationrelatedtothesoft-gelformulationofLPV/r,theapplicationwaswithdrawnbythecompany.OtheroppositionsarependingdecisionsbytheIndianpatentoffice.

Ifoneofthesepatentapplicationsisgranted,currentgenericcompetition,whichisbringingpricessubstantiallydownasdemandincreases,willbeunderthreat.

Indiaandothercountriescouldissuecompulsorylicencestoenableunrestrictedcompetitionfromgenericmanufacturerstocontinue.

InThailand,whereAbbottholdspatents,thepriceofLPV/rwasUS$2,200ppyin2007.InJanuary2007,theMinistryofPublicHealthissuedacompulsorylicencetoimportmoreaffordablegenericversionsofthedrugfromIndia.53ThailandfacedfiercecriticismfromdevelopedcountriesandmultinationalpharmaceuticalcompaniesandAbbott’sresponsewastowithdrawallregistrationapplicationsinThailandforitsnewproducts,includingtheheat-stableLPV/r.ThailandtodayimportsgenericLPV/rfromIndiafor$793ppy.54

InresponsetoThailand’scompulsorylicence,Abbottreducedthepricefor40middle-incomecountriesforboththesoft-gelandtheheat-stableversionto$1,000ppy,includingBrazilwhichatthetimewaspaying$1,380.152

Indeed,thebasicpatentforLPV/risprotectedinBrazilundertheso-called‘pipelinemechanism’,aprovisioninBrazilianpatentlawdeemedtobeinexcessoftheminimumstandardsforintellectualpropertyprotectionundertheTRIPSAgreement.

In2007,theNationalFederationofPharmacists(Fenafar)–onbehalfoftheBrazilianNetworkfortheIntegrationofPeoples(Rebrip)-requestedtheBrazilianProsecutorGeneralconsideroverturningthepipelinemechanismasunconstitutional.TheyarguethatthesepatentsshouldnotbegrantedinBrazilonthebasisthattheyhadnotgonethroughtheregularanalysisprocessforpatentapplicationsandthattheygoagainstthepublicinterest.In2009,theProsecutorGenerallodgedacaseforunconstitutionalitywiththeSupremeCourt.MSF-Brazilisactivelyfollowingthecase.153

Paediatrics LPV/risapprovedforuseinchildrenfromtwoweeksold.17

Inearly2007,AbbottreleasedapaediatricLPV/r100/25mgheat-stabletablet.Whilethisnewformulationiswelcome,itdoesnothelptheyoungestpatients,asthetabletis15mmlongandcannotbecrushed,leavingthisformulationunsuitableforchildrenwhocannotswallowtablets.

Thealternativeforthesesmallchildrenisasolutionthatrequiresrefrigerationuntildispensing,afterwhichitmustbestoredbelow25°Cfornomorethansixweeks.Furthermore,thesolutionconsistsof42%alcoholandhasaveryunpleasanttaste.

Thereisanurgentneedformoreadaptedheat-stablepaediatricformulationofLPV/r(suchassolublegranulesorsprinkles)foryoungchildrenwhocannotswallowtheexistingtablet.Aheat-stablesprinkleinapaediatricdoseisunderdevelopmentbygenericcompanies.ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofaLPV/r40/10mgheat-stablesprinkletobeahighpriority.137

Todaytherearetwogenericsourcesofheat-stableLPV/r100/25mgincludedintheWHOListofPrequalifiedMedicinalProducts.

RecentchangesintheWHOguidelinesrecommendingthatallHIV-positivechildrenunderoneyearofagestartARVtherapyassoonaspossibleregardlessofclinicalstatus,combinedwiththerecommendationtostartallchildrenexposedtonevirapineonaPI-basedregimen,shouldresultinanincreaseddemandforthiscombinationforveryyoungchildren.130

��


GENERAL INFORMATION



•Originatorcompanyandproductbrandname:Roche,Viracept.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):March1997.17

NELFINAVIR ( NFV )

•Deletedfromthe16theditionoftheWHOModelListofEssentialMedicines(EML).26

•Worldsalesoforiginatorproduct:2004:US$259million.After2004,therearenosalesfigureslistedinthecompany’sannualreport.154

•Thebasicpatentwasappliedforin1994byAgouronPharmaceuticalsInc.,155andisduetoexpirein2014.AgouronPharmaceuticalsisnowasubsidiaryofPfizer.NFVwasdevelopedbyAgouronaspartofajointventurewithJapanTobacco,Inc.NFVissuppliedbyRocheoutsidetheU.S.,CanadaandJapan.156

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/gram.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.


AsofApril2010,therewasnogenericsourceofNFV250mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Thelowestavailablegenericpriceisthereforeshownhere.

RochequotespricesinSwissFrancs(CHF),whichwereconvertedtoUS$onthedatereceived.FluctuationsintheUS$/CHFratewillthushaveanimpactonpricesusedinthegraph.

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pp

y

Month/Year

3500

3000

2500

2000

1500

1000

500

0


generic priceNFV 250mg tablet

945

1566

3139

2924

Dailydose

Roche

CiplaCategory1countries

Category2countries


NFV50mg/goralpowder 24g 2129 (0.243/g)

2462 (0.281/g)

NFV250mgtablet 10 1566 (0.429)

2427 (0.665)

945(0.259)

NE

LF

INA

VIR

( N

FV

)P

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IN

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PI )


NE

LF

INA

VIR

( NF

V )

PR

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S ( P

I )


Nelfinavir(NFV)istheonlyproteaseinhibitor(PI)thatdoesnotrequireboostingwithritonavir(RTV).

Thelargepillburden(10tabletsadayforanadult)anditshighpricemakeitaless-desirableoptionwhenselectingaPI.

InJune2007,RocherecalledallbatchesofNFVduetohighlevelsofEthylMethaneSulphonate(EMS),aby-productofthemanufacturingprocessandaknowncarcinogeninanimals.Roche’smarketinglicenceforNFVwassuspendedinEuropeandtheWHOprequalificationprojecttemporarilysuspendedtheproduct.InSeptember2007,thesuspensionswereliftedandmarketinglicencesreinstated.157

Asaresultoftherecall,manypatientswerechangedtoanotherPI.ItisunknowniftherewillcontinuetobedemandfortheNFVformulationinthefuture.NFVwasalsodeletedfromthe16theditionoftheWHOModelListofEssentialMedicines(EML).

PatentsEventhoughpatentscouldnotbeappliedforinIndiapriorto1995,AgouronappliedforpatentsonNFVinmanyotherdevelopingcountries.Thisfactorcontributestothehighpriceofthedrug,togetherwiththesmalldemand.

TherecallofRoche’sNFVin2007highlightstheriskassociatedwithrelyingonasingleproducerforamedicine.

PaediatricsTheuseofNFVoralpowderinchildrenisextremelycomplex.Toobtainthecorrectdosefora10kgchild,12goftheoralpowdermustbemixedwithwater.Accesstoclean,safewaterisoftennotensuredinalldevelopingcountries.

NotonlyisthepaediatricNFVformulationill-adapted,butitspriceremainsprohibitive,asisthecasewithotherproteaseinhibitors.


RITONAVIR ( r or RTV )

GENERAL INFORMATION


AsofApril2010,therewasnogenericsourceofRTV100mgsoft-gelcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Thelowestavailablegenericpriceisthereforeshownhere.

Oct 01

Dec 02

Jun02

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pp

y

Month/Year

4000

3500

3000

2500

2000

1500

1000

500

0


generic price

RTV 100mg capsule (soft-gel)

3504

108323

83


•Worldsalesoforiginatorproduct:2004:US$194million;2003:$93million;and2002:$122million.158After2004,therearenosalesfigureslistedinthecompany’sannualreport.

•ThebasicpatentwasappliedforbyAbbottin1993.159Subsequently,AbbottappliedforpatentsrelatedtopolymorphicformsofRTV 149,160andtoasoft-gelcapsuleformulation.161Theseareduetoexpirerespectivelyin2019and2020.

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/tablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.


•Indicatedforsecond-lineasabooster,foradults,adolescentsandchildren.8,137

•Originatorcompanyandproductbrandname:AbbottLaboratories,Norvir.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):March1996fortheoralsolutionandJune1999forcapsules.17

RIT

ON

AV

IR (

r o

r R

TV

)P

RO

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ASE

IN

HIB

ITO

RS (

PI )

Dailydose,usedasbooster

Abbott Cipla


RTV80mg/mloralsolution - (0.093/ml)

RTV100mgsoft-gelcapsule 2 83 (0.114)

323(0.442)

RTV100mgheat-stabletablet 283(0.114)


RIT

ON

AV

IR ( r

or R

TV

)P

RO

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ASE

INH

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OR

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I )


Ritonavir(RTV)isofcrucialimportanceforthescaling-upandmanagementofsecond-linetreatment,asallproteaseinhibitors(PIs)(withtheexceptionofnelfinavir(NFV)),mustbeboostedwiththisdrug.

Abbotthasdevelopedaheat-stablefixed-dosecombinationoflopinavirandRTV(LPV/r)thatwasapprovedintheU.S.in2005.However,ittookuntilearly2010forAbbotttofinallyreceiveU.S.FDAandEMAapprovalforaheat-stableformulationofRTV100mgtablet,12yearsafterRTVsoft-gelcapsulefirstreceivedregulatoryapproval.

Themarketauthorisationofaheat-stableversionofritonavirasaseparatepillfinallyendsboththestrangleholdbyAbbottonthetreatmentoptionsavailabletopeoplelivingwithHIV/AIDSandthemedicaldoublestandardsthecompanyhaspromotedbyfailingtoprioritisethedevelopmentofsaferversionsofitsmedicines.AsaresultofAbbott’sinaction,manypeoplelivingwithHIVhavebeendeprivedofadditional,improvedandvitaltreatmentoptionsformanyyears.

TheregistrationofthisnewformulationindevelopingcountrieswillbecrucialtoallowtheuseofotherPIsthanlopinavir.

Patents

AlthoughthebasicpatentdisclosingRTVcouldnotbeappliedforinIndia,Abbott’soriginalpatentapplicationsanddivisionalapplicationsonnewformsofRTVarependingbeforetheIndianpatentoffice.Apre-grantoppositiontoanapplicationrelatedtoapolymorphofRTVwasfiledbycivilsocietyorganisationsinIndiainSeptember2006.151ThedecisionoftheIndianpatentofficeispending.TheoutcomeofthisoppositionwillbecrucialtothemanagementofPI-basedsecond-linetreatment.

PatentsrelatedtopolymorphicformsofRTVhavealsobeenfiledinothermiddle-incomecountriessuchasChinaandBrazilwheretheyarepending.InBrazil,ritonavirislocallyproduced,asthebasicpatentisbeingopposedbyBraziliangenericmanufacturersintheCourts.

On14April2010,EcuadorissueditsfirstcompulsorylicenceallowingEskegroupSA,thelocaldistributorforCipla,tomanufacture,offerforsale,sell,useorimportRTV,orcompositionsincludingRTV,forpublicnon-commercialuse,againstthepaymentofroyaltiestoAbbott,untilthepatentexpirationdatein2014.162

ThecompulsorylicencefollowedadecreeofEcuadorianPresidentRafaelCorreainOctober2009,declaringaccesstoessentialmedicinesofpublicinteresttotheEcuadoreanpopulationandallowingthenationalintellectualpropertyofficetoissuecompulsorylicencestothisend,basedonArticle31oftheTRIPSAgreement.163

AccordingtotheMinistryofHealth,thecompulsorylicencealreadyhasyieldedsavingsofUS$150,000tothegovernment.

PaediatricsRTVisapprovedforuseinchildrenandthereisaliquidformulationavailable.Thesolutionhasabitteraftertasteandis43%alcohol,andhencenotadaptedforchildren.

ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofaRTV50mgheat-stablesprinkleortablettobeahighpriority.137


GENERAL INFORMATION



•Originatorcompanyandproductbrandname:Roche,Invirase.


AsofApril2010,therewasnogenericsourceofSQV200mghardcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Thelowestavailablegenericpriceisthereforeshownhere.

RochequotespricesinSwissFrancs(CHF),whichhavebeenconvertedtoUS$onthedatereceived.FluctuationsintheUS$/CHFratewillthushaveanimpactonpricesusedinthegraph.

SAqUINAVIR ( SqV )

Jun02

Dec 02

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2000

1800

1600

1400

1200

1000

800

600

400

200

0


generic priceSQV 200mg hard capsule

13421212

1335

1621




•ThebasicpatentwasappliedforbyRochein1990164andisduetoexpireinDecember2010incountriesnotgrantingpatentextensions.

•ApatentrelatedtooraldosageformwasappliedbyRochein2004andisduetoexpirein2024.165

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/tablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose

Roche


Category2countries


SQV200mghardcapsule 10* 1212 (0.332)

2427 (0.665)

1621(0.444)

SQV500mgtablet 4* 1113 (0.762)

2427 (1.662)

*ThedoseofSQVmustbeboostedwithRTV100mgtwiceaday.

SA

qU

INA

VIR

( S

qV

)P

RO

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ASE

IN

HIB

ITO

RS (

PI )



InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).Assaquinavir(SQV)wasnotidentifiedasoneofthepriorityproducts,itsuseinthedevelopingworldwillbelimited.9

SQV/rappearstobeslightlylesspotentthantheotherboostedPIsandintheoriginalformulationhasahighpillcount(10capsules).141In2004,Rochemarketeda500mgtabletofSQVintheU.S.thatreducedthepillcountfrom10tabletstofour.Whilethisnewformulationshouldimproveadherence,itisonlyregisteredandmarketedinselecteddevelopingcountries.

Aswithotherproteaseinhibitors,SQV’shighpricecontinuestobeabarrier.Solidcompetitionandeconomiesofscaleamongproducersareminimal,asitsuseisfairlylimited.

SQV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.

TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingSQV.

PatentsThebasicpatentwasrejectedinBrazilwherethismedicineislocallyproduced.ItwashowevergrantedinmanyothercountriesincludingChina,SouthAfricaandOAPIcountries.

PatentsrelatedtotheoraldosageformarependinginBrazilandChina.TheyhavebeengrantedinIndiaandSouthAfrica.

PaediatricsSQVhasnotbeenapprovedforuseinchildrenintheU.S.andthereisnopaediatricformulationavailable.

SA

qU

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V )

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I )


TIP

RA

NA

VIR

( T

PV

)P

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IN

HIB

ITO

RS (

PI )

TIPRANAVIR ( TPV )

GENERAL INFORMATION


InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).Astipranavir(TPV)wasnotidentifiedasoneofthepriorityproducts,itsuseinthedevelopingworldwillbelimited.9

BoehringerIngelheimwasinvitedtocontributeapriceforthispublicationandhascommunicatedthattipranavir(TPV)isavailablethroughitsCompassionateUseProgramandthatthecompanyiscurrentlyfilingforregistrationinvariouscountries.

TPV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.

RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.

TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingTPV.

OnefurtherlimitationconcerningTPVisthatthecapsulesrequirerefrigerationuntildispensing.

Patents

TPVpatentshavebeenfiledforwidelyindevelopingcountrieswithgenericproductioncapacity,suchasBrazilandChina.39

InBrazil,wherethepatentapplicationsareunderreview,thedrugregulatoryagency(ANVISA),whichhastogive‘priorconsent’foranypatentapplicationrelatedtoamedicine,hasadvisedfortherejectionofthebasicpatentapplication.170

Inearly2007,civilsocietyexpressedconcernsoverthedelaystotheregistrationprocedureofTPVinBrazil(themedicinehadbeentestedinBrazilianpatientsin14researchcentressinceFebruary2004,butthedrugwasnotactuallyregisteredinthecountry).Afterconsiderablecivilsocietypressure,theregistrationwaseventuallyfiledwithANVISAattheendofFebruary2008,almostthreeyearsafterU.S.FDAandEMAapprovals.TheinterventionbyBraziliancivilsocietywaspartlybasedinresponsetosuspicionsthatBoehringerIngelheimdidnotwanttoregistertheproductinthecountry,unlesstheyhadtheguaranteethatthepatentwouldbegrantedbythepatentoffice.171,172

Paediatrics

TPViscurrentlyapprovedforuseinchildrenfromtwoyearsofageandolder,andapaediatricoralsolutionexists.17

PRICE INFORMATIONBoehringer Ingelheim was invited to contribute a price for this publication and has communicated it does not offer a reduced price for developing countries.

•Therapeuticclass:ProteaseInhibitor(PI).


•TPVisindicatedforcombinationtreatmentofHIV-1infectedadultpatientswhoaretreatment-experiencedandinfectedwithHIV-1strainsresistanttomorethanoneproteaseinhibitor.166

•Originatorcompanyandproductbrandname:BoehringerIngelheim(BI)Pharmaceuticals,Aptivus.

•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):June2005.17



•ThebasicpatentwasappliedforbyUpjohninMay1995,167andisduetoexpirein2015.In1998,Pharmacia&UpjohnappliedforadditionalpatentsrelatedtopharmaceuticalformulationssuitablefortheoraladministrationofTPV.168,169InJanuary2000,BIacquiredworldwiderightsforTPV.

��


GENERAL INFORMATION

ABACAVIR/ LAMIVUDINE ( ABC/�TC )

Dailydose

ViiV Aurobindo(CF) Cipla Matrix(CF)


ABC/3TC60/30mgtablet 4 175 (0.120)

244 (0.167)

ABC/3TC600/300mgtablet 1484(1.326)

134 (0.367)

152(0.417)

Continued overleaf


•Therapeuticclass:doublefixed-dosecombinationoftwoNRTIs.

•Indicatedforfirst-andsecond-lineforchildrenandaspartoftripleNRTIdrugsunderspecificconditionsinadults,adolescentsandchildren.8,137

•Originatorcompany,andproductbrandname:GlaxoSmithKline(GSK),Kivexa(EU),Epzicom(U.S.).InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjoint

venturefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):August2004.17

•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthe

developmentofappropriatenewfixed-dosecombinations.26

•Worldsalesoforiginatorproduct:2009:US$834million;2008:$721million;2007:$641million;2006:$475million;2005:$233million.77,79,80,81,82

•Mostpatentsonabacavir(ABC)orlamivudine(3TC)alsoaffectthiscombination.Inaddition,GSKappliedforpatentsmorespecificallyrelatedtothecombination.173Thepatentexpirydatesrelatedtothiscombinationare2016intheU.S.and2019inEU.82

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AsofApril2010,therewasonegenericsourceofABC/3TC600/300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.

Therehasbeenadecreaseof47%inthegenericpricesince2006.

Jun 06 Jun 07 Jun 08 Jun 10Dec 09

US$

pp

y

Month/Year

800

700

600

500

400

300

200

100

0


generic price

ABC/3TC 600/300mg tablet

255

678

134

484


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ThiscombinationislikelytofalloutoffavoursincethelatestWHOguidelinesforadultsandadolescentsrecommendalineconsistingofeitherAZTorTDF.ItremainsanimportantcombinationforthetreatmentofpaediatricHIV,however.

PatentsGlaxoSmithKlinecouldnotapplyforbasicpatentsrelatedtoabacavir(ABC)orlamivudine(3TC)insomedevelopingcountriessuchasIndiathatdidnotgrantpatentsonpharmaceuticalproductsatthetime.ThisallowedIndiandrugmanufacturerstodevelopgenericversionsofeachmedicine,andofthecombinationofthetwo.

However,GSKwidelyappliedforpatentsinotherdevelopingcountrieswherepossible.

PaediatricsThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofascoredadultfixed-dosecombinationofABC/3TC300/150mgtablet,foruseinchildrenweighingover25kg,tobeahighpriority.137

ViiVdoesnotproduceafixed-dosecombinationofthesedrugsforchildren–eventhoughtheFDCsexistforadults.Nevertheless,forchildrenwhoneedthiscombination,therearetwogenericsourcesincludedintheWHOListofPrequalifiedMedicinalProducts.

ThePaediatricAntiretroviralWorkingGroupofWHOalsoconsidersthedevelopmentofatriplefixed-dosecombinationofabacavir/lamivudine/nevirapine60/30/50mgtablettobeahighpriority.137

Abacavir/Lamivudine ( ABC/3TC ) continued


LAMIVUDINE/ STAVUDINE ( �TC/d�T )

GENERAL INFORMATION

•Therapeuticclass:doublefixed-dosecombinationoftwoNRTIs.

•Indicatedforfirst-lineinchildrenanditisrecommendedtomoveawayfromd4Tinfirst-lineinadultsandadolescents.8,137

•WHOupdatedthe2006guidelinestorecommendareductionindoseofd4Tfrom40to30mgforallweightcategoriesofpatients.107

•TheWHOExpertCommitteeon

theSelectionandUseofEssential

Medicinesrecommendsandendorses

theuseoffixed-dosecombinations

andthedevelopmentofappropriate

newfixed-dosecombinations.26

•Includedinthe16theditionWHO

ModelListofEssentialMedicines

(EML)–onlythed4T30mg

presentation.26

•Individualpatentsonlamivudine(3TC)orstavudine(d4T)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofbothmedicinesincombination,ortotheFDC.


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Continued overleaf


AsofApril2010,thereweresixgenericsourcesof3TC/d4T150/30mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombination,thepriceshownfortheoriginatorproductisthesumofthetwoindividualoriginatorproducts.

Therehasbeena39%decreaseintheoriginatorpriceanda66%decreaseingenericpricesince2003.

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

200

180

160

140

120

100

80

60

40

20

0


generic price

3TC/d4T 150/30mg tablet

42

112125

183


Dailydose

Aurobindo(CF) Cipla(CF) Hetero Matrix(CF) Ranbaxy Strides


3TC/d4T30/6mgdispersibletablet 4 47 (0.032)

3TC/d4T60/12mgdispersibletablet 2 40 (0.055)

3TC/d4T150/30mgtablet 2 50 (0.068)

42 (0.057)

51(0.070)

42 (0.058)

42 (0.058)

44 (0.060)



Thiscombinationhasbeenanimportantformulationthathasfosteredtreatmentscale-upinresource-limitedsettings.


Lamivudine/Stavudine ( 3TC/d4T ) continued

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Wecanthereforeexpecttoseeadecreaseintheuseofthisformulationinthefuture.

PatentsGenericcompaniesincertaindevelopingcountrieswereabletodevelopthesefixed-dosecombinationsbecausepatentsontheindividualproductsdidnotexist.

Thefixed-dosecombinationisnotavailableindevelopedcountriesorincountriessuchasChina,however,whereoneorbothmedicinesisunderpatent.

Paediatrics

Themostcommonlyusedfirst-

lineregimensforchildrentoday

areeither3TC+d4T+NVPor

AZT+3TC+NVP.Withbothofthese

regimens,thereisaneedtostart

nevirapine(NVP)atalowerdose

forthefirsttwoweekstominimise

thesideeffects.

Forchildrenwhoneedthisdouble

3TC/d4Tfixed-dosecombination,

therearetwogenericproducts

includedintheWHOListof

PrequalifiedMedicinalProducts.


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AsofApril2010,therewereninegenericsourcesof3TC/d4T/NVP150/30/200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombination,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.

Therehasbeenadecreaseof76%inthegenericpricesince2002.

LAMIVUDINE/STAVUDINE/ NEVIRAPINE ( �TC/d�T/NVP )

GENERAL INFORMATION

•Therapeuticclass:triplefixed-dosecombinationoftwoNRTIsandaNNRTI.

•Indicatedforfirst-lineforchildrenanditisrecommendedtomoveawayfromd4T-basedfirst-lineinadultsandadolescents.8,137

•WHOupdatedthe2006guidelinestorecommendareductionindoseofd4Tfrom40to30mgforallweightcategoriesofpatients.107

•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML)–onlythed4T30mgpresentation.26

•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26

•Individualpatentsonlamivudine(3TC),stavudine(d4T)ornevirapine(NVP)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatingtotheuseofthemedicinesincombinationortothefixed-dosecombination.CiplafirstdevelopedtheFDCandappliedforpatentsinseveralAfricancountries.


Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

700

600

500

400

300

200

100

0


generic price

3TC/d4T/NVP 150/30/200mg tablet

67

281331

615


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Continued overleaf

Dailydose

Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides


3TC/d4T/NVP30/6/50mgdispersibletablet

4 55 (0.038)

3TC/d4T/NVP60/12/100mgdispersibletablet

2 53 (0.072)

3TC/d4T/NVP150/30/200mgtablet

2 67 (0.092)

67 (0.092)

73 (0.100)

67 (0.092)

70 (0.096)

73 (0.100)



ThiscombinationislikelytofalloutoffavoursincethelatestWHOadultsandadolescentsguidelinesrecommendedanAZT-orTDF-basedfirst-lineregime.

InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsanddevelopaplantomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9


PatentsCiplawasabletodevelopthiscombinationbecausenoneoftheindividualcomponentswerepatentedinIndia.Manyothergenericmanufacturershavefollowedsuitinotherdevelopingcountries,suchasThailand,wherethemedicineswerenotpatented.

ExtensivecompetitionfromnumerousgenericmanufacturershasmadethiscombinationthemostaffordabletripleARVcombinationtreatmenttodate.

PaediatricsThisisoneofthemost-commonlyusedfirst-lineregimensforchildrentoday.

ThePaediatricWorkingGroupatWHOhasreleasedclearguidanceontheidealstrengthofeachoftheindividualARVsinthesefixed-dosecombinations,andtodaytherearetwoformulationsincludedonWHOListofPrequalifiedMedicinalProducts.90

Lamivudine/Stavudine/Nevirapine ( 3TC/d4T/NVP ) continued

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AsofApril2010,therewasonegenericsourceof3TC/d4T+EFV150/30+600mgco-packincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.Asthereisnooriginatorco-pack,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.

Thecombinedpriceoftheoriginatorproductsfor3TC/d4T+EFV150/30+600mghasdecreasedby11%since2006.Thegenericco-packincludedintheWHOListofPrequalifiedMedicinesisafurther13%cheaperthanthesumoforiginatorproducts.

LAMIVUDINE/STAVUDINE + EFAVIRENZ ( �TC/d�T + EFV )

GENERAL INFORMATION

•Therapeuticclass:twoNRTIs+oneNNRTIinaco-pack.

•Indicatedforfirst-lineforchildrenanditisrecommendedtomoveawayfromd4Tbasedfirst-lineinadultsandadolescents.8,137

•WHOupdatedthe2006guidelinestorecommendareductionindoseof



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d4Tfrom40to30mgforallweightcategoriesofpatients.107

•IncludedintheWHOModelListofEssentialMedicines(EML)-onlythed4T30mgpresentation.26

•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinations

andthedevelopmentofappropriatenewfixed-dosecombinations.26

•Individualpatentsonlamivudine(3TC),stavudine(d4T)orefavirenz(EFV)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofthemedicinesincombination,ortotheFDC.

Jun 06 Jun 07 Jun 08 Dec 09 Jun 10

US$

pp

y

Month/Year

450

400

350

300

250

200


generic price

3TC/d4T + EFV 150/30 + 600mg co-pack

394

274

349

304

InDecember2009,WHOreleased

newrecommendationsfor

antiretroviraltherapyforHIVin

adultsandadolescents.Thesenew

recommendationsadvisecountriesto

phaseoutstavudine-basedregimens

becauseoftheirlong-termirreversible

sideeffectsandtomovetowards

zidovudine(AZT)ortenofovir(TDF)-basedfirst-lineregimens.9


PatentsGenericcompaniesincertaindevelopingcountrieswere

abletodevelopthisco-blisterbecausepatentsontheindividualcomponentscontainedinthecombinationdidnotexist.

ThisproductisthusnotavailableindevelopedcountriesorinChinabecauseofvariouspatentson3TC,d4Tand/orEFV.

Dailydose Cipla(CF) Ranbaxy Strides(CF)


3TC/d4T+EFV150/30+600mgtablets(co-pack)

1kit(3tablets)

274(0.751)

304 (0.833)

106(0.290)

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonekit(3tablets).ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.


TENOFOVIR DISOPROxIL FUMARATE/EMTRICITABINE ( TDF/FTC )

GENERAL INFORMATION

•Therapeuticclass:oneNtRTI+oneNRTIinadoublefixed-dosecombination.

•Indicatedforfirst-lineandsecond-lineforadultsandadolescents.8

•Originatorcompanyandproductbrandname:Gilead,Truvada.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):August2004.17


AsofApril2010,thereweretwogenericsourcesofTDF/FTC300/200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

Since2007,therehasbeena48%decreaseinthegenericprice.

US$

pp

y

Month/Year

400

350

300

250

200

150

100

50

0Feb05

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10


generic price

TDF/FTC 300/200mg tablet

362

315

274

143



•Worldsalesoforiginatorproduct:2009:US$2.49billion;2008:$2.11billion;2007:$1.59billion;2006:$1.19billion;2005:$568million;2004:$68million.93,96

•Mostpatentsrelatedtotenofovir(TDF)ortoemtricitabine(FTC)alsoaffectthiscombination.Inaddition,Gileadappliedforpatentsspecificallyrelatedtothiscombinationin2004,whichareduetoexpirein2024.58


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Dailydose

Gilead

Aurobindo(CF) Cipla Hetero Matrix(CF)Category1countries

Category2countries


TDF/FTC300/200mgtablet 1 315 (0.863)

540 (1.479)

155 (0.425)

158(0.433)

164(0.450)

143 (0.392)




Thiscombinationislikelytobewidelyusedindevelopingcountriesasabackboneinfirst-andsecond-lineregimens.


Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.

Itishowevertimeforcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepillonceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9

Forsecond-linetreatment,TDFincombinationwithlamivudine(3TC)oremtricitabine(FTC)aretherecommendedNRTIbackbones,tobeaddedtoaboostedproteaseinhibitor,ifstavudineorzidovudinehavebeenusedinthefirst-lineregimen.

TDFisalsoactiveagainstHepatitisBVirus(HBV)andthereforeplaysanimportantroleinco-infectedpatients.ForHIVpatientsalsorequiringtreatmentforHepatitisB,thefirst-andsecond-linetreatmentshouldcontainTDFandeither3TCorFTC.

Today,therearetwogenericsourcesofthiscombinationincludedintheWHOListofPrequalifiedMedicinalProducts.

Patents

ThiscombinationisproducedbyIndiangenericcompaniesbecauseneitheroftheindividualcomponentsispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF.IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.



ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI–Brazilianpatentoffice)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasrequestedadivisional

patent,whichhasbeenopposedbycivilsocietygroups.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.

InBrazil,Gileadhasalsofiledapatentapplicationforthefixed-dosecombinationTDF/FTC.Ifthepatentisgranted,genericcompetitionwillbestifledonanyessentialcombinationincludingTDF/FTC,beitasadoublefixed-dosecombinationorasatriplefixed-dosecombination,withforexampleefavirenz,lopinaviroratazanavir.FollowingoppositionstothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandSouthAfrica,allowingthemtomanufactureandexportgenericversionsofGilead’sproductstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103

ManufacturersthathavesignedtheseagreementsareunabletosupplycountriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,Brazilistodaypaying$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129

Suchlicensingagreementscancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,butshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.

Paediatrics

Tenofovirisapprovedforadolescentsfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovirandemtricitabine.

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GENERAL INFORMATION

•Therapeuticclass:oneNtRTI+oneNRTI+oneNNRTIinatriplefixed-dosecombination.

•Indicatedforfirst-lineforadultsandadolescents.8

•Originatorcompaniesandproductbrandname:Gilead/Bristol-MyersSquibb/Merck,Atripla.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):July2006.17



AsofApril2010,therewasonegenericsourceofTDF/FTC/EFV300/200/600mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.

Oververyshorttime,since2007,thegenericpricehasdecreasedby55%,whiletheoriginatorpricehasremainedthesame. U

S$ p

py

Month/Year

700

600

500

400

300

200

100

0Jun 07 Jun 08 Dec 09 Jun 10


generic price

TDF/FTC/EFV 300/200/600mg tablet

613613

487

219

TENOFOVIR DISOPROxIL FUMARATE/EMTRICITABINE/EFAVIRENZ (TDF/FTC/EFV)


•Worldsalesoftheoriginator:2009:US$2.382billion;2008:$1.572billion;2007:$903million;2006,$164million(theproductenteredthemarketinthethirdquarteroftheyear).96

•Mostpatentsrelatedtotenofovir(TDF),emtricitabine(FTC),TDF/FTCortoefavirenz(EFV)alsoaffectthiscombination.Inaddition,GileadandBMSjointlyappliedforpatentsspecificallyrelatedtothiscombinationin2006,59whichwouldlastuntil2026.

•GileadpaysroyaltiestoBMS(andconsequentlyMerck)fortheEFVportion,originallyownedbyDupontMerck,whichwassubsequentlyacquiredbyBMS.

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Dailydose

Gilead/BMS/Merck

Cipla Matrix(CF)Category1countries

Category2countries


TDF/FTC/EFV300/200/600mgtablet 1 613 (1.680)

1033 (2.830)

268(0.733)

219 (0.600)



ispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF,includingtheonespecificallyrelatedtothiscombination.176IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.



ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasalsorequestedadivisionalpatentforthepreviouslyrejectedpatent.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.

InBrazil,Gileadhasalsofiledapatentapplicationforthefixed-dosecombinationTDF/FTC.Ifthepatentisgranted,genericcompetitionwillbestifledonanyessentialcombinationincludingTDF/FTC,beitasadoublefixed-dosecombinationorasatriplefixed-dosecombination,withforexampleefavirenz,lopinaviroratazanavir.

FollowingoppositionstothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandoneinSouthAfrica,allowingthemtomanufactureandexportgenericversionsofGilead’sproductstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103

ManufacturersthathavesignedtheseagreementsareunabletosupplycountriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,BrazilistodaypayingUS$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129


PaediatricsTenofovirisapprovedforadolescentfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovir,emtricitabineandefavirenz.


Thisisthefirstone-pill-a-dayfixed-dosecombination,whichmakesitwell-adaptedtoresource-poorsettings.

InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.9


Itistime,however,forcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/FTC/EFV(orTDF/3TC/EFV).Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9

Inaddition,efavirenz(EFV)isthepreferredNNRTIforuseinpatientsstartingARTwhileontuberculosistreatment.

Today,thereisonegenericsourceofTDF/FTC/EFVwhichisincludedintheWHOListofPrequalifiedMedicinalProducts.

PatentsThiscombinationisproducedbyIndiangenericcompaniesbecausenoneoftheindividualcomponents

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TENOFOVIR DISOPROxIL FUMARATE/LAMIVUDINE ( TDF/�TC )

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GENERAL INFORMATION


•Therapeuticclass:NtRTI+NRTIinadoublefixed-dosecombination.

•Indicatedforfirst-andsecond-lineforadultsandadolescents.8



•Mostpatentsrelatedtotenofovir(TDF)ortolamivudine(3TC)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedfor,morespecificallyrelatedtotheuseofthesemedicinesincombination,ortothisspecificFDC,suchasbyCipla.177

Dailydose Cipla Hetero(CF) Matrix(CF)


TDF/3TC300/300mgtablet 1122(0.333)

128 (0.350)

107 (0.294)



AsofApril2010,thereweretwogenericsourcesofTDF/3TC300/300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombinationthepriceshownfortheoriginatorproductisthesumofthetwoindividualoriginatorproducts.

Since2006,thegenericpricehasdroppedby90%whilethecombinedoriginatorpriceofthetwoindividualproductshasdecreasedby3%.ThemostaffordablegenericFDCis60%lessexpensivethanthesumoftheoriginatorproducts.

US$

pp

y

Month/Year

1200

1000

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600

400

200

0Jun 07Jun 06 Jun 08 Dec 09 Jun 10


generic price

TDF/3TC300/300mg tablet

268276

107

1034



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Itishowevertimeforcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepillonceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9

Forsecond-linetreatment,TDFincombinationwithlamivudine(3TC)oremtricitabine(FTC)aretherecommendedNRTIbackbones,tobeaddedtoaboostedproteaseinhibitor,ifstavudineorzidovudinehavebeenusedinthefirst-lineregimen.

TDFisalsoactiveagainstHepatitisBVirus(HBV)andthereforeplaysanimportantroleinco-infectedpatients.ForHIVpatientsalsorequiringtreatmentforHepatitisB,thefirst-andsecond-linetreatmentshouldcontainTDFandeither3TCorFTC.

Today,therearetwogenericsourcesofthiscombinationincludedintheWHOListofPrequalifiedMedicinalProducts.

PatentsThiscombinationisproducedbyIndiangenericcompaniesbecausenoneoftheindividualcomponentsispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF.IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.



ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI–Brazilianpatentoffice)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasrequestedadivisional

patent,whichhasbeenopposedbycivilsocietygroups.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.




PaediatricsTenofovirisapprovedforadolescentsfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovirandlamivudine.

ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofofafixed-dosecombinationofTDF/3TC75/75mgtabletandascored300/300mgtablettobeahighpriority.137


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TENOFOVIR DISOPROxIL FUMARATE/ LAMIVUDINE/EFAVIRENZ ( TDF/�TC/EFV )

��

US$

pp

y

Month/Year

600

500

400

300

200

100

0Jun 07 Jun 08 Dec 09 Jun 10


generic price

TDF/3TC/EFV 300/300/600mg tablet

505

176

513

426

GENERAL INFORMATION

•Therapeuticclass:oneNtRTI+oneNRTI+oneNNRTIinatriplefixed-dosecombination.

•Indicatedforfirst-lineforadultsandadolescents.8

•Includedin16theditionoftheWHOModelListofEssentialMedicines(EML).26

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetabletco-pack.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.


•Mostpatentsrelatedtotenofovir(TDF),lamivudine(3TC)ortoefavirenz(EFV)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofthesemedicinesincombination,ortothisspecificFDC.


AsofApril2010,therewasonegenericsourceofTDF/3TC/EFV300/300/600mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.Asthereisnooriginatorfixed-dosecombinationorco-pack,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.

Oververyshorttime,since2007,thegenericpricehasdroppedby59%.


Dailydose Cipla Matrix(CF)


TDF/3TC/EFV300/300/600mgtablet

1219(0.600)

176 (0.483)




InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyfor HIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.9


Itistime,however,forcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepillonceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9

Inaddition,efavirenz(EFV)isthepreferredNNRTIforuseinpatientsstartingARTwhileonTBtreatment.

Today,thereisonegenericsourceofTDF/3TC/EFVincludedintheWHOListofPrequalifiedMedicinalProducts.

TEN

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PatentsThiscombinationisproducedbyIndiangenericcompaniesbecausenoneoftheindividualcomponentsispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF.IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.



ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI)publishedthepatentrejectionforTDFon

30June2009.However,Gileadhasalsorequestedadivisionalpatentforthepreviouslyrejectedpatent.




PaediatricsTenofovirisapprovedforadolescentfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovir,lamivudineandefavirenz.

��


ZIDOVUDINE/ LAMIVUDINE ( AZT/�TC )

Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

800

700

600

500

400

300

200

100

0


generic price

AZT/3TC 300/150mg tablet

197

730

270

110

�0

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AsofApril2010,therewereninegenericsourcesofAZT/3TC300/150mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.

CompetitionamongWHOprequalifiedsourcescontinues,andhasledtoasteadydecreaseinpricesoftheoriginatorproductby73%andthegenericby59%since2001.

GENERAL INFORMATIONGENERAL INFORMATION

•Therapeuticclass:twoNRTIsindoublefixed-dosecombination.


•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Combivir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):September1997.17



•Worldsalesoftheoriginator:2009:US$649million;2008:$713million;2007:$888million;2006:$1billion;2005:$1.1billion;2004:$1.1billion.77,78,79,80,81,82

•Mostpatentsrelatedtozidovudine(AZT)ortolamivudine(3TC)alsoaffectthiscombination.Inaddition,GSKappliedforpatentsspecificallyrelatedtotheuseofAZTand3TCincombination,178andforthetabletformulationoftheFDC,179whichareduetoexpirein2012and2017,respectively.

Dailydose

ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides



AZT/3TC60/30mgtablet

4 95 (0.065)

121 (0.083)

88(0.060)

AZT/3TC300/150mgtablet

2 197 (0.270)

112 (0.154)

111 (0.152)

115 (0.158)

110 (0.150)

110 (0.150)

131 (0.180)




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OV

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InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.9

Forsecond-linetreatment,AZTincombinationwithlamivudine(3TC)orFTCistherecommendedNRTIbackbone,tobeaddedtoaboostedproteaseinhibitor,iftenofovirhasbeenusedinthefirst-lineregimen.

PatentsGenericversionsofthiscombinationweredevelopedincountrieswhereneitherofthemolecules,northeircombination,

werepatented.However,thegenericversionsofthemedicineproducedinIndiacameunderthreatwhenIndiabegangrantingpatentsonpharmaceuticalsin2005,asGlaxoSmithKline(GSK)hadappliedforapatentonthecombination.

CivilsocietyorganisationsinIndiaopposedthepatentapplicationinMarch2006,127whichresultedinGSKcommunicatinginAugust2006thatpatentsspecificallyrelatedtothefixed-dosecombinationwerebeingwithdrawninallcountries.180

Yetinsomecountries,genericversionsoftheFDCarenotavailablebecauseofGSKpatentrights.InChina,forexample,GSK’sexclusiverightson3TCalonehaveledtothefactthatonlytheoriginatorproductisavailableatUS$1,839perpatientperyear.

PaediatricsThemostcommonlyusedfirst-lineregimensforchildrentodayareeitherAZT+3TC+NVPord4T+3TC+NVP.Withbothoftheseregimens,thereisaneedtostart

theNVPatalowerdoseforthefirsttwoweekstominimisethesideeffects.

Quality-assureddoublefixed-dosecombinationsarethereforeofgreatvalueinallowingchildrentobesafelyandaccuratelydosedwhilestartingtreatment.Intheirabsence,thealternativeistousetwodifferentsyrups,whichcanbedifficulttoadminister.Today,therearetwopaediatricAZT/3TCfixed-dosecombinationtabletsincludedintheWHOListofPrequalifiedMedicinalProducts.

��


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ZIDOVUDINE/LAMIVUDINE/ABACAVIR ( AZT/�TC/ABC )

��

GENERAL INFORMATION

•Therapeuticclass:threeNRTIsintriplefixed-dosecombination.

•Indicatedunderspecificconditionsinadults,adolescentsandchildren.8,137


•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Trizivir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):November2000.17

•Worldsalesoforiginatorproduct:2009:US$307million;2008:$350million;2007:$455million;2006:$529million;2005:$598million;2004:$635million.77,78,79,80,81,82

•Mostpatentsonzidovudine(AZT),lamivudine(3TC),AZT/3TCorabacavir(ABC)alsoaffectthiscombination.Inaddition,GSKappliedforpatentsmorespecificallyrelatedtothetriplecombination.173


Dailydose

ViiV Cipla Matrix Ranbaxy


AZT/3TC/ABC60/30/60mgtablet

4244 (0.167)

AZT/3TC/ABC300/150/300mgtablet

2653 (0.895)

414(0.567)

365(0.500)

548 (0.750)

Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

3000

2500

2000

1500

1000

500

0


generic price

AZT/3TC/ABC 300/150/300mg tablet

653

548

1648

2409


AsofApril2010,therewasonegenericsourceofAZT/3TC/ABC300/150/300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.

Therehasbeenadecreaseof67%inthegenericpriceand73%intheoriginatorpricesince2001.


ZID

OV

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INE

/L

AM

IVU

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E/A

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ThisFDCistheonlytripleNRTIformulationavailable.

Thiscombinationisnolongerapreferredregimeninthedevelopedworld.181

Inthedevelopingworld,itsuseislimitedtoindividualswithcontra-indicationtoNNRTI-basedregimensorwhoareunabletotoleratethem.Thisappliesparticularlyforpeopleco-infectedwithTB/HIV,pregnantwomen,patientswithchronicviralHepatitisandthosewithHIV-2infection.137

PatentsGlaxoSmithKline(GSK)couldnotapplyforbasicpatentsrelatedto

abacavir(ABC),zidovudine(AZT)orlamivudine(3TC)insomedevelopingcountriessuchasIndia,whichdidnotgrantpatentsonpharmaceuticalsatthetime.ThisallowedIndiangenericcompaniestodevelopgenericversionsofeachmedicine,andofthecombination.

However,GSKwidelyappliedforpatentsinotherdevelopingcountries,wherepossible.

InIndia,GSKhadappliedforpatentsmorespecificallyrelatedtothefixed-dosecombination.Thecompanywithdrewthepatentapplicationafterapre-grantoppositionwasfiledin2006.182

PaediatricsThepaediatricformulationofAZT/3TC/ABCisagenericversionandisnowincludedintheWHOListofPrequalifiedMedicinalProducts.

However,thisproductisnotcommerciallyavailableyetbecausethereisnotenoughmarketdemandtomaketheproductcommerciallyviable.


ZID

OV

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ZIDOVUDINE/LAMIVUDINE/NEVIRAPINE ( AZT/�TC/NVP )

GENERAL INFORMATION

•Therapeuticclass:twoNRTI+oneNNRTIintriplefixed-dosecombination.

•Indicatedforfirst-lineforadults,adolescentsandchildren.8,137



•Mostpatentsrelatedtozidovudine(AZT),lamivudine(3TC),AZT/3TCortonevirapine(NVP)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofthesemedicinesincombination,orforthisspecificFDC.

��

Dailydose

Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides


AZT/3TC/NVP60/30/50mgdispersibletablet

4 158 (0.108)

183(0.125)

AZT/3TC/NVP300/150/200mgtablet

2 148 (0.203)

137 (0.188)

155 (0.213)

143 (0.196)

145 (0.199)

139(0.190)



Oct 01

Dec 02

Jun02

Dec03

May03

Feb05

Apr04

Jun06

Jun05

Jun 07

Jun 08

Dec09

Jun10

US$

pp

y

Month/Year

1600

1400

1200

1000

800

600

400

200

0


generic price

AZT/3TC/NVP 300/150/200mg tablet

137

419 441

1356


AsofApril2010,thereweresixgenericsourcesofAZT/3TC/NVP300/150/200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombinationorco-pack,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.

Genericpriceshavesteadilydecreasedby67%since2002.


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Formanyyears,thestavudine-

containing(d4T)regimenhas

playedacrucialroleinARTscale-up

inresource-limitedsettings,due

toitsavailabilityinafixed-dose

combinationand,mostimportantly,

itslowcost.d4Tremainsawidely-

usedARVinfirst-lineregimens.

InDecember2009,WHOreleased

newrecommendationsfor

antiretroviraltherapyforHIVin

adultsandadolescents.Thesenew

recommendationsadvisecountries

tophaseoutstavudine-based

regimensbecauseoftheirlongterm

irreversiblesideeffectsandtomove

towardszidovudineortenofovir-

basedfirst-lineregimens.9

PatentsInadditiontothegenericmanufacturersreferencedabove,ApotexalsomanufacturesanAZT/3TC/NVPfixed-dosecombination183forexporttodevelopingcountriesunderthe30August2003WorldTradeOrganizationdecisiononcompulsorylicensingforexport.184

Inearly2004,MSFmadetheoriginalrequestforthedevelopmentofthisFDCtoApotex,asnogenericversionsoftheFDCwereavailableatthetime.185

MSF,however,ultimatelyendedupprocuringtheFDCfrommanufacturersinIndia,whichreachedthemarketearlierbecausetheIndianmanufacturerswerenothamperedbytheproceduralrequirementsofthenewWTOrulesonCLforexport.

PaediatricsThemost-commonlyusedfirst-lineregimensforchildrentodayareeitherAZT+3TC+NVPord4T+3TC+NVP.

TodaythereisonlyonegenericpaediatricAZT/3TC/NVPfixed-dosecombinationincludedintheWHOListofPrequalifiedMedicinalProducts.

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ZIDOVUDINE/LAMIVUDINE + EFAVIRENZ ( AZT/�TC + EFV )

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Formanyyears,thed4T-containingregimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.

InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountries


tophaseoutstavudine-basedregimensbecauseoftheirlongtermirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.

Inaddition,efavirenz(EFV)isthepreferredNNRTIforuseinpatientsstartingARTwhileonTBtreatment.9

PatentsBasicpatentsrelatedtozidovudine(AZT),lamivudine(3TC)orefavirenz(EFV)couldnotbeobtainedinsome

developingcountriessuchasIndia,whichdidnotgrantproductpatentsonpharmaceuticalsatthetime.

ThisallowedIndiandrugcompaniestomanufacturegenericversionsofthemedicinesandtodevelopthisproduct.

However,GlaxoSmithKlineandMerckmayholdpatentsinotherdevelopingcountries,whichcouldpreventtheimportationanduseofthisfixed-dosecombination.

US$

pp

y

Month/Year

600

500

400

300

200

100

0Jun 06 Jun 07 Jun 08 Dec 09 Jun 10


generic price

AZT/3TC + EFV 300/150 + 600mg tablets (co-pack)

189

462451

558

GENERAL INFORMATION

•Therapeuticclass:twoNRTI+oneNNRTIinaco-pack.

•Indicatedforfirst-lineforadults,adolescentsandchildren.8,137


•Mostpatentsrelatedtozidovudine(AZT),lamivudine(3TC),AZT/3TCortoefavirenz(EFV)alsoaffectthiscombination.Inaddition,CiplaappliedforpatentsspecificallyrelatedtotheuseofAZT,3TCandEFVincombination.186


AsofApril2010,therewerethreegenericsourcesofAZT/3TC+EFV300/150+600mgtablets(co-pack)includedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorco-pack,thepriceshownfortheoriginatorproductisthesumofthetwoindividualoriginatorproducts.

Since2006,thepriceofgenerichasdroppedby58%.

PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonekit(3tablets).ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

Dailydose Aurobindo Cipla Ranbaxy Strides


AZT/3TC+EFV300/150+600mgtablets(co-pack)

1kit(3tablets)

231 (0.633)

320(0.877)

322 (0.883)

189 (0.517)


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NE

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F P

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US$

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ANNEx �: SUMMARy TABLE - ALL PRICES ON ONE PAGE

Developing country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofoneunit(tablet,capsule,etc.).ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.

ARVs in alphabetical order

Daily dose Originator company Generic companies

Abacavir (ABC) ViiV Aurobindo Cipla Hetero Matrix Ranbaxy Strides

20mg/mloralsolution 10ml 230 (0.063/ml)

212 (0.058/ml)

113 (0.031/ml)

60mgtablet 4 153 (0.105)

134(0.092)

183 (0.125)

540(0.370)

300mgtablet 2 438 (0.600)

243 (0.333)

207 (0.283)

256(0.350)

219 (0.300)

274 (0.375)

Atazanavir (ATV)*BMS

MatrixCategory1countries

Category2countries

150mgcapsule 2 353 (0.484)

431 (0.590)

200mgcapsule xx (0.602) (0.743)

300mgcapsule 1 256(0.700)

Darunavir (DRV)* Tibotec

300mgtablet 4 1095(0.750)

Didanosine (ddI)BMS

Aurobindo Cipla RanbaxyCategory1countries

Category2countries

2gpowderforreconstitution(finalconcentration10mg/ml)

12ml 276 (12.590/2g)

308 (14.057/2g)

88 (4.000/2g)

25mgtablet 5 212 (0.116)

429 (0.235)

115(0.063)

228(0.125)

50mgtablet xx (0.158) (0.235) (0.079) (0.115)

100mgtablet 4 311 (0.213)

364 (0.249)

194 (0.133)

188(0.129)

242(0.166)

125mgenteric-coatedcapsule 1 110

(0.300)

150mgtablet xx (0.308) (0.345) (0.225) (0.167)

200mgtablet xx (0.267) (0.257)

200mgenteric-coatedcapsule xx (0.383)


(0.611)249 (0.683)

170 (0.467)

103(0.283)


(0.789)322 (0.881)

256 (0.700)

132(0.363)

Efavirenz (EFV)Merck

Aurobindo Cipla Hetero Matrix Ranbaxy StridesCategory1countries

Category2countries

30mg/mlsuspension xx (0.094/ml) (0.151/ml)

50mgcapsule xx (0.083)

50mgtablet xx (0.120) (0.210) (0.083)


200mgcapsule 3 130 (0.119)

134 (0.122)

152(0.139)

118 (0.108)

200mgtablet 3 394 (0.360)

821 (0.750)

146 (0.133)

110 (0.100)

600mgtablet 1 237 (0.650)

657 (1.800)

73 (0.200)

79 (0.217)

82 (0.225)

61 (0.167)

91 (0.250)

62 (0.170)

*TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofthisdrug.


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Emtricitabine (FTC) Aurobindo Matrix

200mgcapsule 163 (0.173)

79 (0.217)

Etravirine (ETV) Tibotec

100mgtablet 4913(0.625)

Fosamprenavir (FPV)* ViiV

50mg/mlsuspension 12ml648(0.148/ml)

700mgtablet 21222(1.674)

Indinavir (IDV)*

Merck

Aurobindo Cipla HeteroCategory1countries

Category2countries

400mgcapsule 4394 (0.270)

686 (0.470)

292(0.200)

422(0.289)

390 (0.267)

Lamivudine (3TC) ViiV Aurobindo Cipla Hetero Matrix Ranbaxy Strides

10mg/mloralsolution

10ml84 (0.023/ml)

29 (0.008/ml)

37 (0.010/ml)

37(0.010/ml)

150mgtablet 264 (0.087)

34 (0.047)

35 (0.048)

33 (0.045)

34 (0.046)

34 (0.047)

37 (0.050)

300mgtablet 124 (0.067)

41(0.113)

38 (0.103)

34 (0.092)

Lopinavir/ ritonavir (LPV/r)

Abbott

Aurobindo Cipla Hetero MatrixCategory1countries

Category2countries

80/20mg/mloralsolution

4ml176 (0.121/ml)

400 (0.274/ml)

100/25mgheat-stabletablet

3165 (0.151)

376 (0.343)

219 (0.200)

228 (0.208)

133/33mgsoft-gelcapsule

6500 (0.228)

1000 (0.457)

609(0.278)

200/50mgheat-stabletablet

4440 (0.301)

1000 (0.685)

475 (0.325)

463(0.317)

493(0.338)

486 (0.333)

Nelfinavir (NFV)

Roche


Category2countries

50mg/goralpowder 24g2129 (0.243/g)

2462 (0.281/g)

250mgtablet 101566 (0.429)

2427 (0.665)

945(0.259)

Nevirapine (NVP)

Boehringer

Aurobindo Cipla Hetero Huahai Matrix Ranbaxy StridesCategory1countries

Category2countries

10mg/mlsuspension 20ml380 (0.052/ml)

533 (0.073/ml)

66 (0.009/ml)

73 (0.010/ml)

200mgtablet 2219 (0.300)

438 (0.600)

39 (0.054)

34 (0.046)

37 (0.050)

34 (0.047)

39 (0.054)

39 (0.053)

37 (0.050)

Raltegravir (RAL)

Merck

Category1countries

400mgtablet 21113(1.525)



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Ritonavir (RTV)Abbott


80mg/mloralsolution xx (0.093/ml)

100mgsoft-gelcapsule 2 83 (0.114)

323(0.442)

100mgheat-stabletablet 2 83(0.114)

Saquinavir (SQV)*Roche


Category2countries

200mghardcapsule 10 1212 (0.332)

2427 (0.665)

1621(0.444)

500mgtablet 4 1113 (0.762)

2427 (1.662)

Stavudine (d4T)BMS


Category2countries

1mg/mlpowderfororalsolution 20ml 51

(0.007/ml)58 (0.008/ml)

58 (0.008/ml)

44 (0.006/ml)

15mgcapsule xx (0.082) (0.093) (0.026) (0.024) (0.025)

20mgcapsule xx (0.089) (0.093) (0.027) (0.025) (0.028)

30mgcapsule 2 48 (0.066)

68 (0.093)

20 (0.028)

26(0.035)

21 (0.029)

24 (0.033)

26 (0.035)

22 (0.030)

Tenofovir (TDF)Gilead


Category2countries

300mgtablet 1 204 (0.559)

360 (0.986)

100 (0.275)

87 (0.237)

103(0.283)

85 (0.233)

152 (0.417)

146(0.400)

Zidovudine (AZT) ViiV Aurobindo Cipla Hetero Matrix Ranbaxy

10mg/mloralsolution 20ml 234 (0.032/ml)

66 (0.009/ml)

80 (0.011/ml)

66(0.009/ml)

60mgtablet 4 115 (0.079)

100mgcapsule xx (0.122) (0.051) (0.050)


300mgtablet 2 161 (0.221)

101 (0.138)

97 (0.133)

100 (0.137)

91 (0.125)

91 (0.125)

ABC/3TC ViiV Aurobindo Cipla Matrix

60/30mgtablet 4 175 (0.120)

244 (0.167)

600/300mgtablet 1 484(1.326)

134 (0.367)

152(0.417)

3TC/d4T Aurobindo Cipla Hetero Matrix Ranbaxy Strides

30/6mgdispersibletablet 4 47 (0.032)

60/12mgdispersibletablet 2 40

(0.055)

150/30mgtablet 2 50 (0.068)

42 (0.057)

51(0.070)

42 (0.058)

42 (0.058)

44 (0.060)

3TC/d4T/NVP Aurobindo Cipla Hetero Matrix Ranbaxy Strides

30/6/50mgdispersibletablet 4 55

(0.038)

60/12/100mgdispersibletablet 2 53

(0.072)

150/30/200mgtablet 2 67 (0.092)

67 (0.092)

73 (0.100)

67 (0.092)

70 (0.096)

73 (0.100)



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3TC/d4T + EFV Cipla Ranbaxy Strides

150/30+600mgtablets(co-pack)

1kit(3tabs)

274(0.751)

304 (0.833)

106(0.290)

TDF/FTC

Gilead

Aurobindo Cipla Hetero MatrixCategory1countries

Category2countries

300/200mgtablet 1315 (0.863)

540 (1.479)

155 (0.425)

158(0.433)

164(0.450)

143 (0.392)

TDF/FTC/EFV

BMS/Gilead/Merck

Cipla MatrixCategory1countries

Category2countries

300/200/600mgtablet 1613 (1.680)

1033 (2.830)

268(0.733)

219 (0.600)

TDF/3TC Cipla Hetero Matrix

300/300mgtablet 1122(0.333)

128 (0.350)

107 (0.294)

TDF/3TC/EFV Cipla Matrix

300/300/600mgtablet 1219(0.600)

176 (0.483)

AZT/3TC ViiV Aurobindo Cipla Hetero Matrix Ranbaxy Strides

60/30mgtablet 495 (0.065)

121 (0.083)

88(0.060)

300/150mgtablet 2197 (0.270)

112 (0.154)

111 (0.152)

115 (0.158)

110 (0.150)

110 (0.150)

131 (0.180)

AZT/3TC/ABC ViiV Cipla Matrix Ranbaxy

60/30/60mgtablet

4244 (0.167)

300/150/300mgtablet 2653 (0.895)

414(0.567)

365(0.500)

548 (0.750)

AZT/3TC/NVP Aurobindo Cipla Hetero Matrix Ranbaxy Strides

60/30/50mgdispersibletablet

4158 (0.108)

183(0.125)

300/150/200mgdispersibletablet

2148 (0.203)

137 (0.188)

155 (0.213)

143 (0.196)

145 (0.199)

139(0.190)

AZT/3TC + EFV Aurobindo Cipla Ranbaxy Strides

300/150+600mgtablets(co-pack)

1kit(3tabs)

231 (0.633)

320(0.877)

322 (0.883)

189 (0.517)


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ANNEx �: CONDITIONS OF OFFER By COMPANy

Company Eligibility(countries) Eligibility(bodies) Additionalcomments Deliveryofgoods

Abbott Category1countries:AllAfricancountriesandallUnitedNationsdefinedLeast-DevelopedCountriesoutsideAfrica.

Category2countries:SeeAnnex8formoredetails.

Governmentsandprogrammesfullyfundedbygovernments,UNsystemsorganisations,NGOsandothernot-for-profitinstitutionalprovidersinlow-andlowermiddle-incomecountries.

FOB

Aurobindo Noreportedrestrictions. NGOsandgovernmentalorganisations.

Pricesavailableforabove500,000unitsfortabletpacksandabove10,000unitsfororalsolutions.

Deliveryofgoodsfourtosixweeksfromthedateofconfirmedorders.

Paymentbyletterofcredit.

FOBHyderabad(India).

BoehringerIngelheim(BI)

Category1countries:AllLDCs,alllow-incomecountriesandallofAfrica

Category2countries:Allmiddle-incomecountriesnotcoveredundercategory1.

Governments,NGOsandotherpartnerswhocanguaranteethattheprogrammeisruninaresponsiblemanner.

CIF

Bristol-MyersSquibb(BMS)

Category1countries:Sub-SaharanAfricancountries(exceptsouthernAfricancountries)pluscountriesclassifiedaslow-incomebytheWorldBank(exceptKorea,Kyrgyzstan,MoldovaandUzbekistan).

Category2countries:SouthernAfricancountries.Seeannex7formoredetails.

Forotherdevelopingcountries,pricesarenegotiatedonacase-by-casebasiswithBMSlocalrepresentatives.

Bothprivateandpublicsectororganisationsthatareabletoprovideeffective,sustainableandmedically-soundcareandtreatmentofHIV/AIDS.

Category1countriesareinvoicedinUS$.

Category2countriesareinvoicedinSouthAfricanRand.

CIPincoterm.


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Cipla Noreportedrestrictionsbuthigherpriceshavebeennegotiatedseparatelyfor10LatinAmericancountries.

Norestrictions. Noquantity-relatedconditions.Pricesforlargerquantitiesarenegotiable.

FOBMumbai(India)orCIF.

Theactualfreightischargedseparately.

Gilead Thereareover130eligiblecountries,includingallAfricanstatesandadditionalcountriesclassifiedaslow-orlowermiddle-incomebasedonacountry’seconomicstatusmeasurebygrossnationalincome(GNI)andHIVprevalence.SeeAnnex9formoredetails.

Forothercountries,pricesarenegotiatedonacase-by-casebasis.

OrganisationsthatprovideHIVtreatmentin130countriesarecoveredbytheGileadAccessProgram.

TheProgramismanagedthroughGilead’sInternationalAccessOperationsandGilead’slocaldistributionpartners.

Pleasenotethatlocaltaxes,tariffs,andlimiteddistributormark-upsmaybeaddedtotheex-factoryprices.

Shippingtermsvarybylocaldistributor.

Hetero Noreportedrestrictions. Privatesector,publicsectorandNGOs.

Pricesmaybenegotiatedonindividualbasisaccordingtocommercialterms.

FOBMumbai(India).

Huahai Noreportedrestrictions. Governments,non-profitinstitutionalprovidersofHIVcare,NGOs,andotherprivateandpublicorganisationsthatareabletoprovideresponsible,sustainableandmedicallysoundcare.

Forfinalpurchase,pricewillbefurthernegotiated,consideringthefactorslikechangesinexchangerate.

FCAShanghai.

Matrix NoreportedrestrictionsexceptCuba,Iran,NorthKorea,Syria,Sudan,Belarus,Myanmar,DRCongoandLiberia,forwhichpriorapprovalfromMylanLabsIncisrequired.

Norestrictions. Minimumorder–Onefullshipper/cartonpacks.

Ex-worksNashik,Indiaorasspecifiedbycustomers.

Merck PleaserefertoAnnex10fortheindividualdrugcountryeligibility.

Governments,internationalorganisations,NGOs,privatesectororganisations(e.g.employers,hospitalsandinsurers).

MerckmayundercertaincircumstancessupplyARVstopatientsthroughretailpharmacies.

CIP

Ranbaxy Noreportedrestrictions,buthigherpriceswerenegotiatedseparatelyfor10LatinAmericancountries.

NGOsandgovernmentsorprogrammessupportedbythem.

Confirmedletterofcreditoradvancepaymentpreferredfornewcustomers.

FOBDelhi(India).


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Roche Category1countries:Allcountriesinsub-SaharanAfricaandallcountriesclassifiedasLeast-DevelopedCountriesbytheUnitedNations.

Category2countries:Low-incomecountriesandlowermiddle-incomecountries,asclassifiedbytheWorldBank.

Governments,non-profitinstitutionalprovidersofHIVcare,NGOs.

CAD(CashAgainstDocuments)30daysatsight.MinimumorderanddeliveryamountpershipmentisCHF10,000.

FCABaselairport(Switzerland)orCIPairportofdestination.

StridesArcolab

Noreportedrestrictions. Governments,non-profitinstitutionalprovidersofHIVtreatment,NGOs.

Paymentbysignedletterofcredit.

FOBBangalore(India).

Tibotec Sub-SaharanAfricaandLeast-DevelopedCountries(LDCs).

Norestrictions. QuestionsregardingpricesappliedintherelatedcountriesneedtobeaddressedtoAspen.

FOB

ViiV

InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.

Least-DevelopedCountries(LDCs)plussub-SaharanAfrica.

AllCountryCoordinationMechanisms(CCM)projectsfullyfinancedbytheGlobalFundtoFightAIDS,TBandMalaria,aswellasprojectsfundedbyPEPFAR.

Forotherlow-andmiddle-incomecountries,publicsectorpricesarenegotiatedonacase-by-casebasis,eitherbilaterallyorthroughtheAcceleratingAccessInitiative.

Governments,aidorganisations,charities,UNagencies,othernot-for-profitorganisationsandinternationalprocurementagencies.

Insub-SaharanAfrica,employersofferingHIV/AIDScareandtreatmentdirectlytotheiruninsuredstaffthroughworkplaceclinicsorsimilararrangements.

SupplyAgreementrequired(forNGOsrequiringfewerthan10patientpackspermonth,thisrequirementmaybewaived).

Allorganisationsmustsupplythepreferentiallypricedproductsonanot-for-profitbasis.

CIP

NOTES:

Theconditionsdetailedinthetableabovewerethosequoteddirectlybythecompanies.Definitionsofeligibilityvaryfromcompanytocompany.Eachoriginatorcompanyestablishesdifferentrestrictionstotheirofferofreducedprices,andclassifiescountriesaccordingtodifferentcategories.SomecompaniesresorttoLeast-DevelopedCountry(LDC)criteriadevelopedbytheUnitedNations,otherstotheUNDevelopmentProgramme’sHumanDevelopmentIndex(UNDPHDI),andothersstilltoWorldBankclassificationsconcerningcountryincome.

Thislackofuniformityleadstosignificantdifferencesintheeligibilityofacountryfordifferentproducts.

Forcompletedetailspleaserefertoannexes3-10.


ANNEx �: LEAST-DEVELOPED COUNTRIES (LDCS)Source:UnitedNations

http://www.un.org/special-rep/ohrlls/ldc/list.htm

Afghanistan;Angola;Bangladesh;Benin;Bhutan;BurkinaFaso;Burundi;Cambodia;CentralAfricanRepublic;Chad;Comoros;CongoDRC;Djibouti;EquatorialGuinea;Eritrea;Ethiopia;Gambia;Guinea;Guinea-Bissau;Haiti;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Mozambique;Myanmar;Nepal;Niger;Rwanda;Samoa;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;Sudan;Tanzania;Timor-Leste;Togo;Tuvalu;Uganda;Vanuatu;Yemen;Zambia.

ANNEx �: HUMAN DEVELOPMENT INDEx (HDI)Source:UnitedNationsDevelopmentProgramme(UNDP)

http://hdr.undp.org/en/media/hdr_20072008_en_complete.pdf

TheHumanDevelopmentIndexispublishedannuallyasapartofUNDP’sannualHumanDevelopmentReport.

Lowhumandevelopment:

Afghanistan;Benin;BurkinaFaso;Burundi;CentralAfricanRepublic;Chad;CongoDRC;Côted’Ivoire;Eritrea;Ethiopia;Gambia;Guinea;Guinea-Bissau;Liberia;Malawi;Mali;Mozambique;Niger;Rwanda;Senegal;SierraLeone;Timor-Leste;Togo;Zambia.

Mediumhumandevelopment:

Algeria;Angola;Armenia;Azerbaijan;Bangladesh;Belize;Bhutan;Bolivia;Botswana;Cambodia;Cameroon;CapeVerde;China;Comoros;Congo;Djibouti;DominicanRepublic;Egypt;ElSalvador;EquatorialGuinea;Fiji;Gabon;Georgia;Ghana;Guatemala;Guyana;Haiti;Honduras;India;Indonesia;Iran;Jamaica;Jordan;Kenya;Kyrgyzstan;LaoPDR;Lesotho;Madagascar;Maldives;Mauritania;Moldova;Mongolia;Morocco;Myanmar;Namibia;Nepal;Nicaragua;Nigeria;Pakistan;OccupiedPalestinianTerritories;PapuaNewGuinea;Paraguay;Philippines;

St.VincentandtheGrenadines;Samoa;SãoToméandPrincipe;SolomonIslands;SouthAfrica;SriLanka;Sudan;Suriname;Swaziland;Syria;Tanzania;Tajikistan;Thailand;Tonga;Tunisia;Turkmenistan;Uganda;Ukraine;Uzbekistan;Vanuatu;VietNam;Yemen.

ANNEx �: SUB-SAHARAN COUNTRIESSource:WorldBankcountryclassification

http://web.worldbank.org/WBSITE/EXTERNAL/DATASTATISTICS/0,contentMDK:20421402~pagePK:64133150~piPK:64133175~theSitePK:239419,00.html#Sub_Saharan_Africa

Angola;Benin;Botswana;BurkinaFaso;Burundi;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea;Guinea-Bissau;Kenya;Lesotho;Liberia;Madagascar;Malawi;Mali;Mauritania;Mauritius;Mayotte;Mozambique;Namibia;Niger;Nigeria;Rwanda;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;Somalia;SouthAfrica;Sudan;Swaziland;Tanzania;Togo;Uganda;Zambia;Zimbabwe.

ANNEx �: WORLD BANk CLASSIFICATION OF ECONOMIESSource:WorldBank

http://web.worldbank.org/WBSITE/EXTERNAL/DATASTATISTICS/0,contentMDK:20421402~pagePK:64133150~piPK:64133175~theSitePK:239419,00.html

Thelistisupdatedeveryyearon1July.Thisversioniseffectivefrom1July2009.

Low-incomeeconomies:

Afghanistan;Bangladesh;Benin;BurkinaFaso;Burundi;Cambodia;CentralAfricanRepublic;Chad;Comoros;CongoDRC;Eritrea;Ethiopia;Gambia;Ghana;Guinea;Guinea-Bissau;Haiti;Kenya;Korea(DemocraticRepublic);Kyrgyzstan;LaoPDR;Liberia;Madagascar;Malawi;Mali;Mauritania;Mozambique;Myanmar;Nepal;Niger;Rwanda;Senegal;SierraLeone;Somalia;Tajikistan;Tanzania;Togo;Uganda;Uzbekistan;VietNam;Yemen;Zambia;Zimbabwe.

Lowermiddle-incomeeconomies:

Albania;Angola;Armenia;Azerbaijan;Belize;Bhutan;Bolivia;Cameroon;CapeVerde;China;Congo;Djibouti;Ecuador;Egypt;ElSalvador;Georgia;Guatemala;Guyana;Honduras;India;Indonesia;Iran;Iraq;Jordan;Kiribati;Kosovo;Lesotho;Maldives;MarshallIslands;Micronesia;Moldova;Mongolia;Morocco;Nicaragua;Nigeria;Pakistan;OccupiedPalestinianTerritories;PapuaNewGuinea;Paraguay;Philippines;Samoa;SãoToméandPrincipe;SolomonIslands;SriLanka;Sudan;Swaziland;Syria;Thailand;Timor-Leste;Tonga;Tunisia;Turkmenistan;Ukraine;Vanuatu.

Uppermiddle-incomeeconomies:

Algeria;AmericanSamoa;Argentina;Belarus;BosniaandHerzegovina;Botswana;Brazil;Bulgaria;Chile;Colombia;CostaRica;Croatia;Cuba;Dominica;DominicanRepublic;Fiji;Gabon;Grenada;Jamaica;Kazakhstan;Latvia;Lebanon;Libya;Lithuania;Macedonia;Malaysia;Mauritius;Mayotte;Mexico;Montenegro;Namibia;Palau;Panama;Peru;Poland;Romania;RussianFederation;Serbia;Seychelles;SouthAfrica;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Suriname;Turkey;Uruguay;Venezuela.

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ANNEx �: BRISTOL-MyERS SqUIBB ELIGIBLE COUNTRIESSource:ThefollowinglistsandnotesarefromcorrespondencewithBMS.

1stCategoryCountries:

Afghanistan;Angola;Bangladesh;Benin;Bhutan;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea;Guinea-Bissau;Haiti;India;Kenya;LaoPDR;Liberia;Madagascar;Mali;Mauritania;Mauritius;Mongolia;Myanmar;Nepal;Nicaragua;Niger;Nigeria;Pakistan;PapuaNewGuinea;Rwanda;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;SolomonIslands;Somalia;Sudan;Tanzania;Timor-Leste;Togo;Tuvalu;Uganda;VietNam;Yemen.

2ndCategoryCountries:SouthernAfricancountries:

Botswana;Lesotho;Malawi;Mozambique;Namibia;SouthAfrica;Swaziland;Zambia;Zimbabwe.

ANNEx �: ABBOTT ELIGIBLE COUNTRIESSource:Abbott’sAccesstoHIVCareProgram

1stCategoryCountries:AfricaandLeast-Developedcountries:

Afghanistan;Algeria;Angola;Bangladesh;Benin;Bhutan;Botswana;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo-Brazzaville;Côted’Ivoire;CongoDRC;Djibouti;EastTimor;Egypt;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea;Guinea-Bissau;Haiti;Kiribati;Kenya;LaoPDR;Lesotho;Liberia;Libya;Madagascar;Malawi;Maldives;Mali;Mauritania;Mauritius;Morocco;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Rwanda;Samoa;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;SolomonIslands;Somalia;SouthAfrica;Sudan;Swaziland;Tanzania;Togo;Tunisia;Tuvalu;Uganda;Vanuatu;Yemen;Zambia;Zimbabwe.

2ndCategoryCountries:

Low-Incomeeconomies(excludingAfricaandtheLDCasdefinedbytheUN):

India;Kyrgyzstan;Mongolia;Pakistan;PapuaNewGuinea;Tajikistan;Uzbekistan;VietNam.

LowerMiddle-Incomeeconomies(excludingAfricaandtheLDCasdefinedbytheUN):

Albania;Armenia;Azerbaijan;Belarus;Bolivia;BosniaandHerzegovina;Brazil;China;Colombia;DominicanRepublic;Ecuador;ElSalvador;Fiji;Georgia;Guatemala;Guyana;Honduras;Indonesia;Jamaica;Jordan;Kazakhstan;FYR-Macedonia;MarshallIslands;Micronesia;Moldova;Montenegro;Nicaragua;Paraguay;Peru;Philippines;Serbia;SriLanka;Suriname;Syria;Thailand;Tonga;Turkmenistan;Ukraine.

ANNEx �: GILEAD ELIGIBLE COUNTRIESSource:GileadAccessProgram

http://www.gilead.com/enabling_access


Low-IncomePricingTier

Afghanistan;Algeria;Angola;Anguilla;AntiguaandBarbuda;Bahamas;Bangladesh;Barbados;Belize;Benin;Bhutan;Bolivia;Botswana;BritishVirginIslands;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Cuba;Djibouti;Dominica;DominicanRepublic;Egypt;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Grenada;Guatemala;Guinea;Guinea-Bissau;Guyana;Haiti;Honduras;India;Indonesia;Jamaica;Kenya;Kiribati;Kyrgyzstan;LaoPDR;Lesotho;Liberia;Libya;Madagascar;Malawi;Maldives;Mali;Mauritania;Mauritius;Moldova,Rep.of;Mongolia;Montserrat;Morocco;Mozambique;Myanmar;Namibia;Nauru;Nepal;Nicaragua;Niger;Nigeria;Pakistan;Palau;PapuaNewGuinea;Rwanda;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Samoa;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;SolomonIslands;Somalia;SouthAfrica;Sudan;Suriname;Swaziland;Syria;Tajikistan;Tanzania;Timor-Leste;Togo;TrinidadandTobago;Tunisia;TurksandCaicos;Tuvalu;Uganda;Ukraine;Uzbekistan;Vanuatu;VietNam;Yemen;Zambia;Zimbabwe.


LowerMiddle-IncomePricingTier

Albania;Armenia;Azerbaijan;Belarus;BosniaandHerzegovina;China;Ecuador;ElSalvador;Fiji;Georgia;Iran;Iraq;Jordan;Kazakhstan;Montenegro;Panama;Paraguay;Peru;Philippines;Serbia;SriLanka;Thailand;Tonga;Turkmenistan.

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ANNEx �0: MERCk & CO. INC. ELIGIBLE COUNTRIESSource:ThefollowinglistsandnotesarefromcorrespondencewithMerck.

Inquiriesaboutpricingforthefollowingcountrieswillbehandledonacase-by-casebasis:Iraq;MarshallIslands;Micronesia;Montenegro;Nauru;Korea(DPR);Palau.

Merck’sPricingPolicyforefavirenzandindinavir


Afghanistan;Angola;Anguilla;AntiguaandBarbuda;Bangladesh;Belize;Benin;Bhutan;Botswana*;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;Dominica;DominicanRepublic;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Grenada;Guatemala;Guinea-Bissau;Guinea;Guyana;Haiti;Honduras;Jamaica;Kenya;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Moldova;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Pakistan;Panama;PapuaNewGuinea;Romania**;Russia;Rwanda;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;SouthAfrica;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Sudan;Suriname;Swaziland;Tanzania;Thailand;Timor-Leste;Togo;TrinidadandTobago;Tuvalu;Uganda;Ukraine;Vanuatu;WesternSamoa;Yemen;Zambia;Zimbabwe.


Albania;Algeria;Armenia;Azerbaijan;Belarus;Bolivia;BosniaHerzegovina;Brazil;Bulgaria;China;Colombia;CostaRica;Ecuador;Egypt;ElSalvador;Estonia;Fiji;Georgia;India;Indonesia;Iran;Jordan;Kazakhstan;Kyrgyzstan;Latvia;Lebanon;Libya;Lithuania;Macedonia;Malaysia;Mauritius;Mexico;Mongolia;Morocco;Nicaragua;Oman;PalestinianTerritories;Paraguay;Peru;Philippines;SaudiArabia;Seychelles;SriLanka;Syria;Tajikistan;Tunisia;Turkey;Turkmenistan;Uzbekistan;Venezuela;VietNam.

*InBotswana,Merckprovidesindinavirandefavirenzfreeofcharge.

**DuetoaspecialpartnershipinRomania,Merckprovidesindinavirandefavirenzata‘no-profitprice’.

Merck’sPricingPolicyforraltegravir


Afghanistan;Angola;Bangladesh;Benin;Bhutan;Botswana;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea-Bissau;Guinea;Haiti;Kenya;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Rwanda;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;SouthAfrica;Sudan;Swaziland;Tanzania;Timor-Leste;Togo;Tuvalu;Uganda;Vanuatu;WesternSamoa;Yemen;Zambia;Zimbabwe.


Algeria;Armenia;Azerbaijan;Belize;Bolivia;Brazil**;China;Colombia;Dominica;DominicanRep.;Ecuador;Egypt;ElSalvador;Fiji;Georgia;Grenada;Guatemala;Guyana;Honduras;India;Indonesia;Iran;Jamaica;Jordan;Kazakhstan;Kyrgyzstan;Lebanon;Moldova;Mongolia;Morocco;Nicaragua;Pakistan;PalestinianTerritories;Peru;Philippines;St.Lucia;St.VincentandtheGrenadines;SriLanka;Suriname;Syria;Tajikistan;Thailand;Tunisia;Turkey;Turkmenistan;Ukraine;Uzbekistan;Venezuela;VietNam.

*InBotswana,Merckprovidesraltegravirfreeofcharge.

**MercknotesthatBrazil‘receivessignificantreducedpricingduetoextraordinarycommitmentintreatingHIV/AIDSpatients.’

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TDF/FTC/EFV300/200/600mg


Afghanistan;Angola;AntiguaandBarbuda;Bangladesh;Belize;Benin;Bhutan;Botswana*;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;Dominica;DominicanRepublic;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Grenada;Guatemala;Guinea-Bissau;Guinea;Guyana;Haiti;Honduras;Jamaica;Kenya;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Moldova;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Pakistan;Panama;PapuaNewGuinea;Rwanda;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;SouthAfrica;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Sudan;Suriname;Swaziland;Tanzania;Timor-Leste;Togo;TrinidadandTobago;Tuvalu;Uganda;Ukraine;Vanuatu;WesternSamoa;Yemen;Zambia;Zimbabwe.


Bolivia;Indonesia;Kyrgyzstan;Mauritius;Mongolia;Nicaragua;Seychelles;Syria;Tajikistan;Uzbekistan;VietNam.


Fordocumentationonpatents:

‘Determiningthepatentstatusofessentialmedicinesindevelopingcountries’,HealthEconomiesandDrugs,EDMSeriesNo.17,UNAIDS/WHO/MSF,2004.http://www.who.int/Intellectualproperty/submissions/MSFSubmissionWHO_EPM_PAR_2004.6.pdf

HIV/AIDSmedicinesandrelatedsupplies:Contemporarycontextandprocurement.Technicalguide.Chapter2andAnnexB.WorldBank,Washington,DC,2004http://siteresources.worldbank.org/INTPROCUREMENT/Resources/Technical-Guide-HIV-AIDS.pdf

‘Drugpatentsunderthespotlight.Sharingpracticalknowledgeaboutpharmaceuticalpatents’MSF,June2004.http://www.who.int/3by5/en/patents_2003.pdf

KnowledgeEcologyInternationalhttp://www.keionline.org,orhttp://www.cptech.org/ip/health/

Fordocumentationonquality:

PrequalificationProgrammemanagedbytheWorldHealthOrganization(WHO)http://apps.who.int/prequal/

ApprovedandTentativelyApprovedAntiretroviralsinAssociationwiththePresident’sEmergencyPlanhttp://www.fda.gov/InternationalPrograms/FDABeyondOurBordersForeignOffices/AsiaandAfrica/ucm119231.htm

Otherusefulwebsitesreferencedinthisdocument:

InternationalDispensaryAssociation(IDA)PriceIndicatorhttp://www.idafoundation.org/documents/ida_hiv_aids_aug_07_zondersnijlijnen.pdf

USFoodandDrugAdministrationOrangeBookhttp://www.fda.gov/cder/ob/

ANNEx ��: SUGGESTED RESOURCES FOR FURTHER INFORMATION:Fordocumentationonpricesquotedbycompanies:

UntanglingtheWebcanalsobefoundonlineatutw.msfaccess.org

BackissuesofUntanglingtheWebofpricereductions:apricingguideforthepurchaseofARVsfordevelopingcountriescanbefoundat:http://www.msfaccess.org/main/hiv-aids/untangling-the-web/untangling-the-web-archive/

SourcesandPricesofSelectedMedicinesandDiagnosticsforPeopleLivingwithHIV/AIDS(June2005and2006)http://www.who.int/medicines/areas/access/med_prices_hiv_aids/en/index.html

GlobalHIV/AidsEpidemicSelectionofAntiretroviralMedicationsProvidedunderU.S.EmergencyPlanIsLimited,January2005:http://pdf.dec.org/pdf_docs/Pcaab266.pdf

Fordocumentationonpricesreportedbycountries:

WHOGlobalPriceReportingMechanismhttp://www.who.int/3by5/amds/price/hdd/

TheGlobalFundPurchasePrice-Reporthttp://pqr.theglobalfund.org/PQRWeb/Reports/PurchasePriceReport.aspx

ManagementSciencesforHealth(MSH)InternationalDrugPriceIndicatorGuidehttp://erc.msh.org/mainpage.cfm?file=1.0.htm&id=1&temptitle=Introduction&module=DMP&language=English#top

WHOAFROregionEssentialMedicinesPriceIndicatorhttp://www.who.int/medicines/publications/afro-essential_med_price_indicator_nocover.pdf

CatalogueofUSFoodandDrugAdministrationApprovedDrugProductshttp://www.accessdata.fda.gov/scripts/cder/drugsatfda/

WHO.AntiretroviraltherapyforHIVinfectioninadultsandadolescents:recommendationsforapublichealthapproach-2006rev.Geneva:WHO;2006.http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf

WHO.Rapidadvice:antiretroviraltherapyforHIVinfectioninadultsandadolescents.Geneva:WHO;2009Nov.http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf

AntiretroviralTherapyforHIVInfectioninInfantsandChildren:TowardsUniversalAccess:Recommendationsforapublichealthapproach2007.http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf

UNICEFProcurementofHIV/AIDSRelatedSupplies.September2007http://www.unicef.org/supply/files/Procurement_of_HA_supplies(1).pdf

Biotechnology/PharmaceuticalsHIV/AIDSIndustryReport–April2005http://www.aethlonmedical.com/pdfs/IndustryReport.pdf

ClintonFoundationAntiretroviralPriceListhttp://www.clintonfoundation.org/files/chai_arv_priceList_april2010_english.pdf

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ANNEx ��: COMPANy CONTACTSAbbott:RobDintruffHIV/AccessDepartmentAbbottLaboratories,AbbottPlace219GolfClubTerraceConstantiaKloof1719,Johannesburg,SouthAfricaTel:+27118582000E-mail:[email protected]

Aurobindo:SharaddJainGMInternationalSales(Formulation)AurobindoPharmaLimitedSurvey#313,BachupallyQutubullapurMandalHyderabad-500072,IndiaTel:+914023044060Ext515(Office)E-mail:[email protected]:www.aurobindo.com

Boehringer Ingelheim:PhilipBaumCDCommunicationsTel:+49613277-2459Fax:+49613277-3829E-mail:[email protected]

Dr.MichaelRabbowCorpCommsCorporateAffairsTel:+49(6132)77-92701Fax:+49(6132)77-6601E-mail:[email protected]

Bristol-Myers Squibb:AllcountrieswiththeexceptionofSouthernAfrica:MrsMarie-AstridMercier,Coordinator,Globalaccessprogram,BMSoffice:ParisE-mail:[email protected]

SouthernAfrica:BMSoffice:JohannesburgMrArchieSmutsTel:+27114566527E-mail:[email protected]

Cipla: Mr.SanjeevGupteGeneralManager-ExportsCiplaLimitedTel:+912223021397(Direct)2309552123092891Fax:+912223070013/23070393/23070385E-mail:[email protected],[email protected]

Gilead: FororganisationsinAfrica,enquiriesshouldbedirectedto:GraemeRobertsonPhoneNumber:+442085872229E-mail:[email protected]:PhoneNumber:+16505225101E-mail:[email protected]:www.gilead.com/access_developing_world

Hetero: BhaveshShahHeteroDrugsLimited607/608MatharuArcard,PlotNo.32,SubhashRoad,VileParle(E),Mumbai–400057,IndiaTel:+912266910809(Office)Tel:+912266922829(Direct)Fax:+912226845709Mobile:+919821044912E-mail:[email protected]:www.heterodrugs.com

Huahai: Mr.CaiMinDaViceGeneralManagerXunqiao,Linhai,Zhejiang317024,ChinaTel:+8657685991657(Headquarters);Tel:+862153086386(Shanghaioffice)E-mail:[email protected]

Matrix: AvrindKandaGeneralManager,BusinessDevelopmentAntiRetroviralFinishedDosagesMatrixLaboratoriesLimited1-1-151/1,VFloor,SairamTowersAlexanderRoad,Secunderabad-500003AndhraPradesh,IndiaTel:+914027700363Fax:+919948220256

SunilGaurBusinessDevelopmentMatrixLaboratoriesLimited1-1-151/1,VIFloor.SairamTowersAlexanderRoadSecunderabad-500003AndhraPradesh,IndiaTel:+914027700363/+914055327722Mobile:+919948092653Fax:+914066336401

Merck: MargalitEdelmanManager,GlobalPublicPolicyMerck&Co.Inc.WS2A-65,OneMerckDrive,P.O.Box100WhitehouseStation,NJ08889-0100Tel:(908)4233112Fax:(908)7351391E-mail:[email protected]

Ranbaxy: ShaileshPednekarGeneralManager-GlobalTherapyManagementandARVBusinessPlotNo90Sector32,Gurgaon122001,IndiaTel:+91.124.41.85.911(DIR),9141.35.000ext5911,+919810263679(mobile)Fax:+91.124.41.66.035E-mail:[email protected]

Roche: SandraTorrianiDemandManagerPTBFPMIF.Hoffmann-LaRocheLtdBuilding237/2.31CH-4070Basel,SwitzerlandTel:+41616889390Fax:+41616871815E-mail:[email protected]

Strides: Mrs.AlokaSenguptaPresident–MarketingStridesHouse,BannerghattaRoadBangalore560076,IndiaTel:+91-80-66580748Mobile:+919845024470Fax:+91-80-66580800E-mail:[email protected]

Dr.RajivAlexVice–President–AT&MStridesHouse,BannerghattaRoadBangalore560076,IndiaTel:+91-80-66580103Mobile:+919632925925Fax:+91-80-66580800E-mail:[email protected]

Tibotec: LucDenysSeniorDirectorWorldwideAccessPrograms,VirologyTibotec-VircoComm.VaTel:+32(0)15.461.018Fax:+32(0)15.401.259Mobile:+32(0)479.96.43.42

ViiV: ScottPurdonPhDDirectorAccessandGovernmentAffairsViiVHealthcare980GreatWestRoadBrentfordMiddlesex,TW89GSUKTel:+442083806228

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ANNEx ��: THE CLINTON FOUNDATION ANTIRETROVIRAL PRICE LIST

(AS OF APRIL �0�0)

SUPPLIERS & PRODUCTSCHAIhasagreementswithsevenmanufacturersofARVformulations,activepharmaceuticalingredientsand/orpharmaceuticalintermediates:AurobindoPharma,CiplaLtd.,HeteroDrugs,MacleodsPharmaceuticals,MatrixLaboratories,RanbaxyLaboratoriesandStridesArcolabs.TheARVsincludedinCHAI’spricingagreementsare:abacavir(ABC),atazanavir(ATV),efavirenz(EFV),emtricitabine(FTC),lamivudine(3TC),lopinavir/ritonavir(LPV/r),nevirapine(NVP),stavudine(d4T),tenofovir(TDF)andzidovudine(AZT).

TERMS & CONDITIONS PriceslistedbelowareavailabletocountriesparticipatingintheCHAIProcurementConsortium,whichcurrentlyincludesover70nations.ThesepricesapplytoprocurementsbynationalgovernmentsthataremembersoftheCHAIProcurementConsortium,ororganizationsprocuringonbehalfofmembergovernments,tosupportpubliccareandtreatmentprograms.Productsshouldbepurchaseddirectlyfrompartnersuppliersorthroughprocurementagentsrepresentingtheaforementionedprograms.

ForTDFproductsofferedbysuppliersunderavoluntarylicensefromGilead,indicatedpricingisavailableonlytocountriescoveredunderthevoluntarylicense.PleasecontactNeerajMohanatnmohan@clintonfoundation.orgwithanyquestionsrelatedtothisissue.AccesstoCHAIpricesassumespromptpaymentfollowingtheshipmentoforders.Purchasersissuingrequestsforpricequotesand/ortenderstowhichCHAIpartnersuppliersareinvitedtorespondshouldreferencemembershipintheCHAIProcurementConsortium,butrequestsandtendersneednotberestrictedtoCHAIpartnersuppliers.

PRICESCHAIpricesrepresentpriceceilingsatorbelowwhichtheindicatedsuppliersmustpricetheirproductswhensellingorcommunicatingpricequotesforthespecifiedproductstomembersoftheCHAIProcurementConsortium.Inestablishingpriceceilings,CHAIaimstoofferthelowestavailablepricestoConsortiummemberswhileensuringthatproductsareavailablefrommorethanonepartnersupplierwhereverpossible.PriceslistedbelowareFCAAirportfromthepointofexport.Perpersonperyearpricesforpediatricformulationsaredeterminedbasedontherecommendeddailydosingfora10kgchild(unlessaformulationisnotrecommendedfora10kgchild,inwhichcasetheannualpriceiscalculatedbasedondosingforanapplicableweightband).

qUALITyCHAIiscommittedtothesustainablesupplyofhigh-qualityARVs,consistentwiththespecificationsofdossiersapprovedbytheWorldHealthOrganization(WHO),U.S.FoodandDrugAdministration(U.S.FDA),orastringentregulatoryauthority(SRA)asdefinedbytheInternationalConferenceonHarmonization(ICH).Inthelistonpages90and91,footnotesspecifytheapplicablequalityassurancestatusforeachformulation:(1)ApprovedbytheWHOPrequalificationProgramme;(2)ApprovedbytheU.S.FDAorotherSRA;(3)SubmittedtotheWHO,U.S.FDAorotherSRAforreviewandrecommendedforprocurementbyExpertReviewPanel(ERP)ofTheGlobalFund;(4)SubmittedtotheWHO,U.S.FDAorotherSRAforreviewbutnotyetrecommendedbyERP.

The Clinton Health Access Initiative (CHAI) supports national governments to expand high-quality care and treatment to people living with HIV/AIDS. CHAI offers reduced prices for antiretrovirals (ARVs) to members of its Procurement Consortium.


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ADULT PRODUCTS CEILING PRICE (USD) SUPPLIER

Nameandstrength Packaging PerYear PerPack PerUnit Aurobindo Cipla Hetero MacLeods Matrix Ranbaxy

3TC(150mg)HDPEbottle60tablets

$32 $2.67 $0.044 a1,2 a1 a1 a2 a1,2

ABC(300mg)HDPEbottle60tablets

$222 $18.50 $0.308 a2 a1,2 a4 a1,2

AZT(300mg)HDPEbottle60tablets

$93 $7.75 $0.129 a1,2 a1 a2 a1,2 a1,2

AZT(300mg)+3TC(150mg)

HDPEbottle60tablets

$110 $9.17 $0.153 a1,2 a1,2 a1,2 a2

AZT(300mg)+3TC(150mg)+NVP(200mg)

HDPEbottle60tablets

$140 $11.67 $0.194 a2 a1,2 a1,2

ATV(300mg)*HDPEbottle30capsules

$265 $22.08 $0.736 a3

d4T(30mg)HDPEbottle60capsules

$24 $2.00 $0.033 a1,2 a2 a1,2 a1

d4T(30mg)+3TC(150mg)

HDPEbottle60tablets

$45 $3.75 $0.063 a1 a1,2 a1,2

d4T(30mg)+3TC(150mg)+NVP(200mg)

HDPEbottle60tablets

$79 $6.58 $0.110 a1 a1,2 a1 a1

EFV(600mg)HDPEbottle30tablets

$75 $6.25 $0.208 a1,2 a1,2

LPV/r(200/50mg)HDPEbottle120tablets

$440 $36.67 $0.306 a2 a2 a4 a1,2

NVP(200mg)HDPEbottle60tablets

$37 $3.08 $0.051 a1,2 a1,2 a1,2 a2 a1,2 a1,2

RTV(100mg)heat-stable*

HDPEbottle30tablets

$90 $7.50 $0.250 a4

TDF(300mg)HDPEbottle30tablets

$87 $7.25 $0.242 a2 a1,2 a2 a1,2

TDF+3TC(300/300mg)*

HDPEbottle30tablets

$110 $9.17 $0.306 a2 a2

TDF+FTC(300/200mg)HDPEbottle30tablets

$140 $11.67 $0.389 a2 a2

TDF+3TC+EFV(300/300/600mg)

HDPEbottle30tablets

$200 $16.67 $0.556 a2

TDF+FTC+EFV(300/200/600mg)

HDPEbottle30tablets

$229 $19.10 $0.637 a2

CLINTON HEALTH ACCESS INITIATIVE — ANTIRETROVIRAL (ARV) PRICE LIST

*CHAIhasnegotiatedapriceofUSD$425perpersonperyearforaco-packagedonce-dailysecond-lineregimencontainingATV,heat-stableRTVandafixeddosecombinationofTDF+3TC.Thisproductislikelytobeavailableforprocurementinlate2010.


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PEDIATRIC PRODUCT CEILING PRICE (USD) SUPPLIER

Nameandstrength Packaging PerYear PerPack PerUnit Aurobindo Cipla Matrix Strides

3TC(50mg/5ml)HDPEbottle240ml

$25 $1.65 $0.007 a2 a1,2

ABC(20mg/ml)HDPEbottle240ml

$203 $13.53 $0.056 a2 a1

ABC60mgHDPEbottle60tablets

$126 $5.25 $0.088 a2 a1

ABC(60mg)+3TC(30mg)HDPEbottle60tablets

$168 $7.00 $0.117 a2 a1

AZT(50mg/5ml)HDPEbottle240ml

$57 $1.90 $0.008 a2 a1,2

AZT(100mg)HDPEbottle100capsules

$35 $4.80 $0.048 a2 a1

AZT(60mg)+3TC(30mg)HDPEbottle60tablets

$80 $3.34 $0.056 a2 a1

AZT(60mg)+3TC(30mg)+NVP(50mg)

HDPEbottle60tablets

$102 $4.25 $0.071 a1

d4T(1mg/ml)HDPEbottle200ml

$47 $1.30 $0.007 a2 a2


$16 $1.35 $0.023 a2


$8 $1.40 $0.023 a2

d4T(6mg)+3TC(30mg)HDPEbottle60tablets

$46 $1.90 $0.032 a2

d4T(12mg)+3TC(60mg)HDPEbottle60tablets

$40 $3.30 $0.055 a2


HDPEbottle60tablets

$55 $2.30 $0.038 a1,2


HDPEbottle60tablets

$52 $4.30 $0.072 a1,2

EFV(50mg)HDPEbottle30tablets

$27 $2.24 $0.075 a2 a2

EFV(200mg)HDPEbottle90capsules

$43 $10.75 $0.119 a2 a2 a2

EFV(200mg)HDPEbottle90scoredtablets

$43 $10.75 $0.119 a1,2

LPV/r(100/25mg)HDPEbottle120tablets

$220 $18.33 $0.153 a1

NVP(50mg/5ml)HDPEbottle240ml

$53 $1.75 $0.007 a1,2 a1

CLINTON HEALTH ACCESS INITIATIVE — ANTIRETROVIRAL (ARV) PRICE LIST


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3TC:lamivudine;nucleosideanaloguereversetranscriptaseinhibitor.

ABC:abacavir;nucleosideanaloguereversetranscriptaseinhibitor.

AIDS:AcquiredImmuneDeficiencySyndrome.

ALP:AIDSLawProject.

ANVISA:AgênciaNacionaldeVigilânciaSanitária(NationalHealthSurveillanceAgencyBrazil).

API:activepharmaceuticalingredient.

ARIPO:AfricanRegionalIntellectualPropertyOrganisation.TherearecurrentlysixteenstateswhicharepartytotheLusakaAgreementandthereforemembersofARIPO.Theseare:Botswana,theGambia,Ghana,Kenya,Lesotho,Malawi,Mozambique,Namibia,SierraLeone,Somalia,Sudan,Swaziland,Tanzania,Uganda,ZambiaandZimbabwe.

ARV:Antiretroviral.

ATV:atazanavir,proteaseinhibitor.

AZT:zidovudine(alsoabbreviatedtoZDV),nucleosideanaloguereversetranscriptaseinhibitor.

BI:BoehringerIngelheim.

BMS:Bristol-MyersSquibb.

Category1:Inthisdocument,‘Category1’isusedtodescribethosecountriesthatareeligibleforthemostdiscountedpriceofferedbyacompany.

Category2:Inthisdocument,‘Category2’isusedtodescribethosecountriesthatarenoteligibleforthelowestpricesreservedforcategory1countries,butareneverthelessofferedadiscountbycompanies.Crucially,thisdiscountisusuallyconsiderablysmallerthanthediscountofferedtocategory1countries.

CCR5:chemokinecoreceptor5.

CF:ClintonFoundation.

AB

BR

EV

IAT

ION

S

ABBREVIATIONS

CHAI:ClintonFoundationHealthAccessInitiative.Since2002,theClintonFoundationHealthAccessInitiative(CHAI)hasassistedcountriesinimplementinglarge-scale,integratedcare,treatmentandpreventionprogrammes.

CHF:Swissfranc.

CIF:‘CostInsuranceandFreight’.Acommercialterm(incoterm)meaningthatthesellerdeliversoncethegoodspasstheship’srailintheportofshipment.ThesellermustpaythecostsandfreightnecessarytobringthegoodstothenamedportofdestinationBUTtheriskoflossordamagetothegoods,aswellasanyadditionalcostsduetoeventsoccurringafterthetimeofdelivery,aretransferredfromthesellertothebuyer.

CIP:‘CarriageandInsurancepaidto...’.Acommercialterm(incoterm)meaningthatthesellerdeliversthegoodstothecarriernominatedbyhim,butthesellermustinadditionpaythecostofcarriagenecessarytobringthegoodstothenameddestination.Thismeansthatthebuyerbearsalltherisksandanyadditionalcostsoccurringafterthegoodshavebeendelivered.However,inCIPtheselleralsohastoprocureinsuranceagainstthebuyer’sriskoflossofordamagetothegoodsduringcarriage.Consequently,thesellercontractsforinsuranceandpaystheinsurancepremium.

CL:compulsorylicence.

d4T:stavudine;nucleosideanaloguereversetranscriptaseinhibitor.

ddl:didanosine;nucleosideanaloguereversetranscriptaseinhibitor.

DDU:‘Delivereddutyunpaid’.Acommercialterm(incoterm)meaningthatthesellerdeliversthegoodstothebuyer,notclearedforimport,andnotunloadedfromanyarrivingmeansoftransportatthenamedplaceofdestination.Thesellerhastobearthecostsandrisks

involvedinshippingthegoods,otherthan,whereapplicable,any‘duty’(whichincludestheresponsibilityfortherisksofthecarryingoutofthecustomsformalities,andthepaymentofformalities,customsduties,taxesandothercharges)forimportinthecountryofdestination.Such‘duty’hastobebornebythebuyeraswellasanycostsandriskscausedbyhisfailuretoclearthegoodsfortheimporttime.

DRV:darunavir,proteaseinhibitor.

EC:enteric-coated.

EFVorEFZ:efavirenz;non-nucleosideanaloguereversetranscriptaseinhibitor.

EMA:EuropeanMedicinesAgency.FormerlyEuropeanAgencyfortheEvaluationofMedicinalProducts.

EML:EssentialMedicinesList.FirstpublishedbyWHOin1977,itservestoidentifyalistofmedicines,whichprovidesafeandeffectivetreatmentforinfectiousandchronicdiseasesaffectingthevastmajorityoftheworld’spopulation.The16thUpdatedListwaspublishedinMarch2009andincludes14antiretroviralsandfivefixed-dosecombinations.

EU:EuropeanUnion.

EXW:‘Ex-works’.Acommercialterm(incoterm)meaningthatthesellerdeliverswhenheplacesthegoodsatthedisposalofthebuyerattheseller’spremisesoranothernamedplace(i.e.works,factory,warehouseetc.)notclearedforexportandnotloadedonanycollectingvehicle.

FDA:UnitedStatesFoodandDrugAdministration.

FDC:fixed-dosecombination–multipledrugscombinedinasinglepill.


FOB:‘Freeonboard’.Acommercial(incoterm)termmeaningthatthesellerdeliverswhenthegoodspasstheship’srailatthenamedportofshipment.Thismeansthatthebuyerhastobearallcostsandrisksoflossordamagetothegoodsfromthatpoint.TheFOBtermrequiresthesellertoclearthegoodsforexport.

FPV:fosamprenavir;proteaseinhibitor.

FTC:emtricitabine;nucleosideanaloguereversetranscriptaseinhibitor.

Genericdrug:AccordingtoWHO,apharmaceuticalproductusuallyintendedtobeinterchangeablewiththeoriginatorproduct,whichisusuallymanufacturedwithoutalicensefromtheoriginatorcompany.

GPRM:WHOGlobalPriceReportingMechanism.AdatabasecontainingpricespaidbyUNICEF,theInternationalDispensaryAssociation(IDA),ManagementSciencesforHealth(MSH)/Deliver,andtheGlobalFundtoFightAIDS,TuberculosisandMalaria.

GSK:GlaxoSmithKline.

HDI:HumanDevelopmentIndex.AsummarycompositeindexcompiledbyUNDP,thatmeasuresacountry’saverageachievementsinthreebasicaspectsofhumandevelopment:longevity(orlifeexpectancyatbirth),knowledge(oradultliteracyrateandenrolmentineducation),andadecentstandardofliving(grossdomesticproductpercapita).

HIV:HumanImmunodeficiencyVirus.

IDV:indinavir;proteaseinhibitor.

IRBM:InstituteforResearchinMolecularBiology.

LDCs:Least-DevelopedCountries,accordingtoUnitedNationsclassification.

LPV/r:lopinavir/ritonavir;boostedproteaseinhibitor.

MSD:MerckSharp&Dome(Merck&Co.,Inc.)

MSF:MédecinsSansFrontières,DoctorsWithoutBorders.

MVC:maraviroc;entryinhibitor.

AB

BR

EV

IAT

ION

S NDRA:NationalDrugRegulatoryAuthority.

NFV:nelfinavir;proteaseinhibitor.

NGO:Non-GovernmentalOrganisation.

NIH:NationalInstitutesofHealth.

NNRTI:Non-NucleosideReverseTranscriptaseInhibitor.

NRTI:NucleosideAnalogueReverseTranscriptaseInhibitor.

NtRTI:NucleotideReverseTranscriptaseInhibitor.

NVP:nevirapine;non-nucleosideanaloguereversetranscriptaseinhibitor.

OAPI:OrganisationAfricainedelaPropriétéIntellectuelle(AfricanIntellectualPropertyOrganisation).MemberstatesincludeBenin,BurkinaFaso,Cameroon,CentralAfricanRepublic,Chad,Congo,Côted’Ivoire,Gabon,Guinea,Guinea-Bissau,EquatorialGuinea,Mali,Mauritania,Niger,Senegal,Togo.

PEPFAR:President’sEmergencyPlanforAIDSRelief,aUnitedStatesprogrammetofightHIV/AIDSindevelopingcountries.

PI:ProteaseInhibitor.

PLHA:PeopleLivingWithHIV/AIDS.

PMTCT:PreventionofMother-to-ChildTransmission.

ppy:perpatientperyear.

r:low-doseritonavir,usedasabooster.

R&D:ResearchandDevelopment.

RAL:raltegravir;integraseinhibitor.

RTV:ritonavir;proteaseinhibitor.

SQV:saquinavir;proteaseinhibitor.

TAC:TreatmentActionCampaign.

TB:tuberculosis.

TDF:tenofovirdisoproxilfumarate;nucleotidereversetranscriptaseinhibitor.

TPV:tipranavir;proteaseinhibitor.

TRIPS:Trade-relatedAspectsofIntellectualPropertyRights.

UN:UnitedNations.

UNAIDS:UnitedNationsJointCosponsoredProgrammeonHIV/AIDS.Createdin1996,tolead,strengthenandsupportanexpandedresponsetotheHIV/AIDSepidemic.ThesixoriginalcosponsorsareUNICEF,UNDP,UNFPA,UNESCO,WHOandtheWorldBank.UNDCPjoinedinApril1999.

UNDP:UnitedNationsDevelopmentProgramme.

UNITAID:isaninternationaldrugpurchasefacilitythatwasestablishedin2006byBrazil,Chile,France,NorwayandtheUnitedKingdomandnowincludes27countriestoprovidenewsourcesoffundingtofightHIV/AIDS,malariaandtuberculosis.

USFDA:UnitedStatesFoodandDrugAdministration.

VL:voluntarylicence.

WHO:WorldHealthOrganization.

WHOGPRM:WHOGlobalPriceReportingMechanism.

WTO:WorldTradeOrganization.

ZDV:zidovudine(alsoabbreviatedtoAZT);nucleosideanaloguereversetranscriptaseinhibitor.


DISCLAIMER:‘UntanglingtheWebofPriceReductions’isapricingguideandcannotberegardedasacompanypricelist.Itiscrucialthatanypurchaserverifypricesandavailabilityaswellasqualitystatusdirectlywiththesupplierbeforeprocurement.MédecinsSansFrontièreshasmadeeveryefforttoensuretheaccuracyofpricesandotherinformationpresentedinthisreport,butMSFmakesnorepresentationsorwarranties,eitherexpressedorimplied,astotheiraccuracy,completenessorfitnessforaparticularpurpose.InclusionofaproductinthisdocumentdoesnotindicateMSFpurchasesorusestheproduct.Informationonpatentstatusoftheproductsmentionedinthisguideisindicativeonlyandnotexhaustive,andshouldbeverifiedwithrelevantnationalpatentofficeswhenusedforotherthanreasonsofgeneralinformation.

ACkNOWLEDGEMENTS:

Frontandbackcoverphotos:BrendanBannon

Design/artwork:ACWLtd+44(0)2083924330www.acw.uk.com

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