1. The Future of HIV Treatment Melbourne – International AIDS Conference
Greg Perry
Melbourne – International AIDS Conference
July 2014

2. 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

3. 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

4. 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

5. 9.7 million have access to treatment
Some Challenges
Accelerating availability of new ARVs in developing countries
Ensuring new ARVs become available in the most suitable formulations
Promoting robust market competition to bring down prices of new treatments
9.7 million have access to treatment

6. Partnering for Innovation and Access
Medicines Patent Pool
Partnering for Innovation and Access
PATENT HOLDERS
MANUFACTURERS
PEOPLE LIVING WITH HIV
Sub-
Licences
Licences
Medicines
ROYALTIES
Established in 2010 with the support of

7. 1. Accelerating Availability of New ARVs in Developing Countries7

8. Long Lag from Originator Market Approval to Generic Availability
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
Timeline From Originator Approval to Generic Availability:
FDA/EMA Approval
Generic Approvals 1 2 3 4 5 6 7 8 9 10
Years
Historically, it has taken an average of 7 – 9 years for generic versions of new HIV treatment to reach LICs after FDA/EMA approval
Could the future look like this?
FDA/EMA Approval
Generic Approvals 1 2 3 4 5 6 7 8 9 10
Years

9. Patents on new ARVs could delay the timeline even further
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
Darunavir `
Lopinavir
Atazanavir
Tenofovir Disproxil Fumarate (TDF)
Fosamprenavir
Maraviroc
Etravirine
Tenfovir Alfenamide Fumarate (TAF)
Rilpivirine
Raltegravir
Elvitegravir
Ritonavir heat-stable
Dolutegravir
Cobicistat
* Secondary patents on some of these products may extend patent protection beyond the date shown.

10. Accelerating availability of new medicines in developing countries through voluntary licensing
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
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
November 2013
2023
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?
* As part of the QUAD

11. 2. Ensuring ARVs Become Available In The Most Suitable Formulations11

12. Licensing to Facilitate Fixed Dose Combinations
No patent
Patented
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, but
licensed to MPP
Within the MPP, patents are “pooled” in one place, easing the development of new FDCs
Patented, but
licensed to MPP

13. ARV Formulations For Children
Current pediatric formulations of HIV medicines are often inappropriate (e.g. alcohol based, bitter liquids, require refrigeration, not available as FDCs).
Simpler treatment options
Suitable for different age groups
Fixed-dose combinations
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

14. The Paediatric HIV Treatment Initiative
Launched in May A UNITAID-MPP-DNDi-CHAI 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

15. 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 negotiations
Black: Compound patent expired or licensed bilaterally
Orange: Not currently licensed
Note: licences cover countries accounting for 87% to 93.4% of PLHIV in developing countries, depending on the licence

16. 3. Promoting Robust Market Competition For New Patented ARVs16

17. Role of market competition in price reduction: case of tenofovir1

18. 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

19. Key Challenge: inclusion of certain middle-income countries in licences
Proportion of people living with HIV by country income category,
Source: UNAIDS, IMF 2012

20. 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