Enteric vaccine development – mixed...
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Enteric vaccine development – mixed fortunes Tony Nelson Department of Paediatrics The Chinese University of Hong Kong
Transcript of Enteric vaccine development – mixed...
Enteric vaccine development –mixed fortunes
Tony NelsonDepartment of Paediatrics
The Chinese University of Hong Kong
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (Thiry)
Other enteric vaccines in the pipeline …
• Novovirus• Shigella• ETEC• Non-typhoidal salmonellas• Camphylobacter• Others
#mixed_fortunes
No one I met at this time — doctors, nurses, practicantes, or fellow-patients —failed to assure me that a man who is hit through the neck and survives it is the luckiest creature alive. I could not help thinking that it would be even luckier not to be hit at all. – George Orwell, Homage to Catalonia
Rotashield®
Temporal association
Murphy TV et al, 2001. New Engl J Med 344: 564-72
Withdrawal of Rotashield®
• Risk of intussusception– highest 3-10D post-
vaccination– ~ 1 in 10,000 – Age related– ? Later compensatory
decrease
• Reinvigorating the competition– Big pharma (GSK, Merck)– Local producers (China/India)
• Parallel testing in both developed & developing countries
Glass. Lancet 2004;363:1547
Lancet's Paper(s) of the Year 2006
"The editors were impressed by the efficacies of these two vaccines, which one day are likely to stand alongside smallpox, measles, and poliomyelitis vaccines in their global public health benefit."
Butcher J. Lancet 2007;369:91-2
Early adopters• United States – Feb 2006• Panama – Mar 2006• Brazil - Mar 2006• Venezuela – Apr 2006 • Mexico – Jun 2006• Nicaragua – Oct 2006• El Salvador – Oct 2006• Australia NT – Oct 2006
Lewis MJ, Oliveira L, PAHO, presentation at WHO, Global Vaccine Research Forum, Dec 2006
WHO Position PaperRotavirus Vaccines
• Clinical efficacy of rotavirus vaccines has been demonstrated mainly in the United States, Europe and Latin America
• WHO strongly recommends the inclusion of rotavirus vaccination into the National Immunization Programmes (NIP) of regions where vaccine efficacy data suggest a significant public health impact and where appropriate infrastructure and financing mechanisms are available
Weekly Epidemiological Record. 2007;82(32):285-296
Industry-RVP partnerships
http://www.who.int/vaccine_research/documents/Session4_Neuzil_presentation.pdf
Efficacy against severe RVGE in 1st
Year of life by mortality quartile
Weekly Epidemiological Record. 2009;84(51-52):533-40
Latin America, Europe, Western Pacific
85-100%4thLow
Vietnam, Latin America72-85%3rd
Bangladesh, South Africa46-72%2ndMiddle
Ghana, Kenya, Malawi, Mali
50-64%1stHigh
CountriesEfficacyMortality Quartile
WHO strata
0
25
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75
100
0 5000 10000 15000 20000 25000 30000 35000 40000 45000 50000
GDP per head purchasing power parity US$ 2007
1-Ye
ar e
ffica
cy %
USA
Singapore (0.9) Hong Kong (0.9) Europe (Finland) (4.4)
South Africa (2.5)Vietnam (1.1)
Kenya (1.7)
Ghana (2.5) Malawi (3.9)
Mali (0)
Bangladesh (2.5) Rotavirus vaccine
efficacy against severe RVGE & cases prevented
per 100 vaccinated
Nelson & Glass. Lancet 2010;376:568-70
SAGE Rotavirus recommendation• Inclusion of rotavirus vaccination of
infants into all national immunization programmes
• In countries where diarrhoeal deaths account for >10% of mortality among children aged <5y, the introduction of the vaccine is strongly recommended
Weekly Epidemiological Record. 2009;84(23):213-236
Rotarix & Porcine circovirus 1(2)
• GACVS considers that the benefits of vaccination far outweigh any currently known risk associated with use of Rotarix
• European Medicines Agency sees no safety concerns with the Rotarix oral vaccine
• FDA – no evidence at this time that this finding poses a safety risk … recommending … temporarily suspend the use of Rotarix
http://www.who.int/vaccine_safety/topics/rotavirus/rotarix_statement_march_2010/en/
Do rotavirus vaccines work in practice?
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (U Parashar)
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (U Parashar)
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (C Kirkwood)
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (C Kirkwood)
40% 60-70% 77%
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (V Richardson)
Intussusception revisited …
• ~1-2/100,000 infants vaccinated• After 1st dose of both vaccines• Not seen in all countries• ? Association with oral polio• GACVS – no change in global RV
vaccine recommendation
Weekly Epidemiological Record. 2011;86(5):37-44
http://www.sabin.org/events/schedule/9th-international-rotavirus-symposium (Wecker)
28 down, 165 to go …
“Fortune truly helps those who are of good judgment.”
Euripides
McKinsey & Co, 2002(World Bank & Gates Foundation)
What decision-makers want to support new vaccine use
• Proven local disease burden• Proven safe and effective vaccine• Convincing health economics• Limited negative effect on existing vaccines• Support from clinical opinion leaders• No blocking from GPs and parents• Funding from external sources
Courtesy Joe Bresee
1 : 205
1 : 50
1 : 5
Risk Events
* Glass R et al. Lancet 2006;368:323-332# Parashar UD et al. JID 2009;200(Suppl 1):S9-15
Global rotavirus disease burden
24 million outpatient visits
2.4 million inpatient visits
114 million episodes
610,000 deaths *, 527,000 deaths #
1 : 1
A wealth of data …
Yes but are rotavirus vaccines good value for
money?
Price of rotavirus vaccine• GAVI-eligible countries
– US$ 0.15 - 0.30 /dose• PAHO
– US$5.5-7.5 /dose (15-16.5 per course)• US price
– US$ 62.50 /dose (2006)• Hong Kong
– US$65 -72 /dose
Madhi SA et al. Bulletin WHO 2008;86(5):365-733 Flannery 9th International Rotavirus Symposium, Joburg Aug 2010
Widdowson MA etal. Pediatrics 2007;119(4):684-97
The cost-effectiveness planeNew intervention more costly
New intervention less costly
New intervention less effective
New intervention more effective
MaximumacceptableICER
Cost-effectiveinterventions
New intervention more effective but more costly
Old intervention dominates
New intervention dominates
New intervention less costly but less effective
Nelson et al. Vaccine 2009;27:F12-7.
Some medical break-even prices of rotavirus vaccine per course
• Low income1 -• Vietnam2 $ 0.94• Low-mid income1 $ 1.06• Kyrgyzstan3 $ 1.30• Egypt4 $ 1.34• Indonesia5 $ 2.70• Upper-mid income1 $ 4.0• USA6 $ 36• Hong Kong7 $ 40-92• Taiwan8 $ 54-60
1Rheingans et al. J Infect Dis. 2009;200(Suppl 1):S16-27.2Fischer TK et al. J Infect Dis. 2005;192:1720-6.3Flem ET et al. J Infect Dis. 2009;200(Suppl 1):S195-202 4Ortega O et al. J Infect Dis. 2009:200(Suppl 1):S92-85Wilopo SA et al. Vaccine 2009;27(S):F67-746Widdowson MA et al. Pediatr 2007;119:684-977Ho AMH et al. Arch Dis Child. 2008;93:52-8.8Wu CL et al. Vaccine 2009;27:1492-9
Yes but these vaccines are not affordable ?
www.dictionary.comaf·ford·a·ble ( P )
adj. That can be afforded: affordable housing; an affordable risk.
af·forda·bili·ty n.af·forda·bly adv.Source: 4th Edition of The American Heritage® Dictionary of the English Language,
affordableadj : that you have the financial means for; "low-
cost housing" [syn: low-cost, low-priced]Source: WordNet ® 2.0, © 2003 Princeton University
Do governments (or parents), in both rich and poor countries, “have the financial means for”
vaccines ?
Are vaccines “affordable”?• What governments see as a “priority” will
determine “affordability”– Vaccines may be cost-effective but if a low priority =
“NOT affordable”
Are vaccines “affordable”?• Likewise what parents see as a “priority” will
determine “affordability”– Vaccines may be perceived as safe & effective but
if a low priority = “NOT affordable”
Vaccine Price
• Negotiable• Governments can negotiate better
than parents• Price in NIP typically much less than
in private sector
Vaccine Procurement Baseline
Proposal for minimum of 0.01% GNI– amount of money individual countries should
spend on own vaccine procurement– “Global Funds” pick up the balance
Mahoney et al. Vaccine 2000;18:2625-35
Cost of GAVI program
Increase under-used (HIB, hep B, yellow fever) & new (pneumo, rota, meng A, JE) vaccines for 72 low-income countries from 2005-2015= $US 1 billion / yr= 0.1% of low-income country GNI= 0.004% of high-income country GNI
3rd GAVI partners meeting, Dec 2005
Official Development Assistance(ODA)
• Undertaken by official sector• Given to developing countries• Promote economic development &
welfare• Concessional (grant element of >25%)
OECD Definition
Resolution 2626: the 0.7% commitment
• October 1970 • United Nations General Assembly• By 1975 developed countries should give
0.7% of GNI as ODA
Unicef. 0.7% Background
Richest Countries
1991
COUNTRY PPP/cap ODA/capUnited States 22130 (42) Richest nationSwitzerland 21780 (168)Germany 19770 (87)Japan 19390 (89)Canada 19320 (92)Hong Kong 18520 +6 Richest recipient of ODAFrance 18430 (137)Denmark 17880 (268) Austria 17690 (68)Belgium 17510 (83)Sweden 17490 (285) Norway 17170 (285) Italy 17040 (71)UAE 17000 (332) Netherlands 16820 (180)Australia 16680 (55)United Kingdom 16340 (54)Finland 16130 (129)Singapore 14734 +7New Zealand 13970 (28)Israel 13460 +405 Recipient of most ODAKuwait 13126 (105) Nelson & Yu. Lancet 1996;348:1642-3
Proposed Definition of Poverty Focused Assistance (PFA)
• Undertaken by official sector• Given to Least developed Countries• Promote social development• Concessional (grant element 100%)
Nelson & Yu. Lancet 1996;348:1642-3
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Denmark
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UNDP 2006
ODA given in 2003 to Least Developed Countries (LDC) for social programs (health & education)
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ODA % Social
UNDP 2006
Total ODA & Poverty Focused Assistance (PFA) 2003
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
Norway
Belgium
Ireland
Denmark
Netherlands
Sweden
United Kingdom
Switzerland
Finland
Canada
Italy
Germany
Australia
United States
Luxembourg
France
Spain
New Zealand
Portugal
Greece
Japan
Austria
% of GNI given as ODA
ODA%GNI 2003 PFA%GNI 2003 UNDP 2006
Some facts & an assumption
1. Vaccines are very cost-effective2. Vaccines as optimal % GNI = 0.01-0.03% 3. Scaling up GAVI = 0.004% GNI4. ODA (donor aid) target 0.7% GNI (most <
0.3% & very little to social programs)
“Therefore persuading governments to scale up ODA for vaccines should be easy if governments & public know the facts ”
Government Vaccine Score Card
1. Vaccines included in NIP & % coverage 2. U5 mortality rate & MGD target3. % GNI spent on vaccines
= Vaccine Procurement Baseline (VPB)4. % GNI given for vaccines (donors only)
= Vaccine Program Assistance (VPA)
Final thoughts
• Vaccines are one of the most cost-effective health interventions
• Prices are negotiable • Documenting % GNI “spent on” & “given
for” vaccines could help advocacy
Thank You
