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

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

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

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

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

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

1. Accelerating Availability of New ARVs in Developing Countries 7

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

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.

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

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

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

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

The Paediatric HIV Treatment Initiative Launched in May 2014. 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

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

3. Promoting Robust Market Competition For New Patented ARVs 16

Role of market competition in price reduction: case of tenofovir 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

Key Challenge: inclusion of certain middle-income countries in licences 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