The Future of HIV Treatment
Greg PerryMelbourne – International AIDS Conference
July 2014
1
The Future of HIV Treatment?All people on treatment have access to the best possible regimens
Treatment side effects are minimal or non-existent
People can stay on the same treatment without developing resistance
Cost is no longer a barrier in determining which treatment to take
The most effective regimens are available as once-daily single tablet regimens or in long-acting formulations
Children have access to the best possible treatment that is suitable for their age
2
Recent progress in HIV treatment
• According to UNAIDS 12.9 million PLHIV were accessing treatment in end 2013
• Drugs with higher toxicity (e.g. d4T) are being replaced with better drugs
• Price of TDF-based first-line treatment has come down significantly in most countries
• Lower cost second line treatments increasingly available in many developing countries
3
New Medicines Being Developed
• 4 new ARVs approved since 2011
• 2 new single tablet regimens since 2011 and more in development
• There are new drugs with lower side effects and potential for being cheaper than current drugs
• Long-acting formulations under study that could enhance treatment options
4
Some Challenges
1. Accelerating availability of new ARVs in developing countries
2. Ensuring new ARVs become available in the most suitable
formulations
3. Promoting robust market competition to bring down prices of
new treatments
9.7 million have
access to treatment
5
PATENT HOLDERS
LicencesSub-Licences Medicines
MANUFACTURERS PEOPLE LIVING WITH HIV
ROYALTIES
Medicines Patent PoolPartnering for Innovation and Access
Established in 2010 with the support of
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1. Accelerating Availability of New ARVs in Developing Countries
77
Long Lag from Originator Market Approval to Generic Availability
FDA/EMA Approval
0 1 2 3 4 5 6 7 8 9 10
Timeline From Originator Approval to Generic Availability:
Generic Approvals
Years
• Time from FDA approval of new ARV molecules to availability of quality assured generics for developing countries has generally been between 5 to 10 years
Could the future look like this?
FDA/EMA Approval
0 1 2 3 4 5 6 7 8 9 10
Generic Approvals
Years8
1985 1990 1995 2000 2005 2010 2015 2020 2025 2030
TRIPS Transition for
Developing Countries TRIPS Transition for Least Developed Countries Zidovudine Didanosine Stavudine Saquinavir Nevirapine Abacavir Emtricitabine Lamivudine Indinavir Efavirenz
Darunavir1985 1990 1995 2000 2005 2010 2015 2020 2025 2030
` Lopinavir Atazanavir Tenofovir Disproxil Fumarate (TDF) Fosamprenavir Maraviroc Etravirine
Tenfovir Alfenamide Fumarate (TAF) Rilpivirine Raltegravir Elvitegravir
Ritonavir heat-stable Dolutegravir Cobicistat 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030
* Secondary patents on some of these products may extend patent protection beyond the date shown.
Patents on new ARVs could delay the timeline even further
9
Accelerating availability of new medicines in developing countries through voluntary licensing
Drug Approval in US (FDA)
Approval in Europe (EMA)
Expiry of main patent
Date of MPP licence
Projected filing for market approval by MPP Sub-licensees(estimate - subject to change)
Cobicistat August 2012*
September 2013
2027 July 2011 mid-2015
Elvitegravir August 2012*
November 2013
2023 July 2011 mid-2015
Dolutegravir August 2013
January 2014
2026 April 2014 2016
Tenofovir Alafenamide Fumarate (TAF)
Not yet approved (in phase III clinical trials)2015 ?
2021 Very soon 2017/2018?
Availability of quality generics can be accelerated by licensing medicines during final phase of development or shortly after approval and managing licences to accelerate development and registration
10* As part of the QUAD
2. Ensuring ARVs Become Available In The Most Suitable Formulations
1111
Licensing to Facilitate Fixed Dose Combinations
• Fixed-dose combinations improve treatment adherence for adults and children alike
• But face particular patent challenges:
• Patents on one component can impact access to entire regimen
• Patents on the combinations
No patent
Patented
Patented
No patent
Patented, but licensed to MPP
• Within the MPP, patents are “pooled” in one place, easing the development of new FDCs
Patented, but licensed to MPP
ARV Formulations For Children
• Simpler treatment options• Suitable for different age groups• Fixed-dose combinations
Current pediatric formulations of HIV medicines are often inappropriate (e.g. alcohol based, bitter liquids, require refrigeration, not available as FDCs).
Key missing formulations identified by WHO Paed AIDS Working Group
• AZT or ABC/3TC/LPV/r • ABC/3TC/EFV• DRV/r• TDF/3TC(or FTC)/EFV)• ATV/r• RAL• DTG based combinations• COBI as an alternative booster to RTV 13
The Paediatric HIV Treatment Initiative
Goal: To ensure that appropriate and affordable medicines are available to the World’s 3.3 million children living with HIV.
Key focus: partner with all stakeholders to:• Share IP and data on formulations
and access • Accelerate development of urgently
needed paediatric ARV formulations• Effectively shape the paediatric HIV
market
Launched in May 2014. A UNITAID-MPP-DNDi-CHAI initiative
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New ARV formulations for adults
Most recently approved single tablet regimens:• TDF/FTC/EVG/COBI• TDF/FTC/RPV
Fixed-dose combinations under development:• ABC/3TC/DTG• TAF/FTC/EVG/COBI• TAF/FTC/DRV/COBI
Other combinations recommended by the CADO 2 Conference for study that could be equally or more potent, durable and affordable than currently recommended treatments:• TAF/3TC(or FTC)/EFV• TAF/3TC(or FTC)/DTG• DTG+DRV/r
Green: Licensed to the MPP
or in negotiationsBlack: Compound patent expired or licensed bilaterallyOrange: Not currently
licensed
Note: licences cover countries accounting for 87% to 93.4% of PLHIV in developing countries, depending on the licence
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3. Promoting Robust Market Competition For New Patented ARVs
1616
Role of market competition in price reduction: case of tenofovir
2006 2007 2008 2009 2010 2011 2012 2013$0.00
$50.00
$100.00
$150.00
$200.00
$250.00
TDF 300mg price
2 34
6 7FDA or WHO-PQ approved generic ver-sion of TDF 300mg
5
8 9
Lowest price for TDF 300mg and number of quality-as-sured generics on the market (not available in all
countries)
1
Medicines Patent Pool Out-Licensing
• MPP
Sublicensees
Aurobindo
Cipla
Desano
Emcure
Hetero
Laurus
Micro Labs
Mylan
Shasun
Shilpa
Promoting robust generic competition through non-exclusive licensing to qualified manufacturers
MPP has licensed 7 ARVs to 10 generic partners:• Tenofovir Disproxil
Fumarate• Emtricitabine• Elvitegravir• Cobicistat• Abacavir paediatric• Atazanavir• Dolutegravir
Currently managing 35 sub-licences
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Key Challenge: inclusion of certain middle-income countries in licences
2000 2010 20200%
20%
40%
60%
80%
100%
70%
37%
13%
High
Upper middle
Lower middle
Low
Income category
Proportion of people living with HIV by country income category, 2000 - 2020
Source: UNAIDS, IMF 2012
One possible approach to address challenge in some MICs
• Market Segmentation (public/private)
– In many countries, national treatment programs cater for vast majority of people on treatment
– Generics able to supply national treatment programs
– Originators continue to cater for small private market
• Introducing royalties that are differentiated according to countries’ socio-economic circumstances
– Enables countries to benefit from robust generic competition which results in lower prices
– Royalty could take into account different variables: GDP per capita, inequality, disease burden, others
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