MPP LICENCES AND OPPORTUNITIES FOR INTRODUCTION OF NEW PRODUCTS AND FORMULATIONS Esteban Burrone, July 2017

To increase access to new treatments for HIV THE MEDICINES PATENT POOL: A PUBLIC HEALTH VOLUNTARY LICENSING ORGANIZATION Founded in 2010 by To increase access to new treatments for HIV And facilitate innovation e.g. combinations and paediatrics In 2015, expanded mandate to Hepatitis C and Tuberculosis

How we work Prioritise medicines Approach patent holders Negotiate public health oriented licences Sub-license to generics Facilitate development of needed formulations Facilitate access to affordable medicines for people in LMICs

LICENSING TERMS AND CONDITIONS “Companies with the most pro-access criteria in their agreed licences have all negotiated agreements through the MPP.” Source: The Access to Medicines Index, 2016

MPP LICENCES: COUNTRIES INCLUDED BY INCOME GROUP Product(s) Licensed LIC LMIC UMIC HIC Undefined Total Abacavir (paed.) 31 53 5 1 121 + Atazanavir 46 29 3 110 + Cobicistat 30 42 18 9 4 103 Daclatasvir 2 112 + Dolutegravir (paed.) Dolutegravir 6 92 + Elvitegravir 17 8 100 Lopinavir/Ritonavir (paed.) 50 19 102 + Lopinavir/Ritonavir (Africa) 26 10 57 + Raltegravir (paed.) 92 Ravidasvir * - 19 + Sutezolid (global) 52 56 79 218 TDF 23 112 TAF

NEW: EXPANSION OF ATAZANAVIR LICENCE Today we are announcing the expansion of our licence with Bristol Myers Squibb (BMS) on WHO recommended 2nd line medicine atazanavir from 110 to 122 countries New countries: Algeria, Morocco, Tunisia, Egypt*, Indonesia*, Malaysia*, Philippines*, Vietnam, Equatorial Guinea, Cook Islands, Niue, Ukraine* These countries are home to 1.4 million people living with HIV We are pleased to be announcing the expansion of the atazanavir licence so that more countries can benefit from access to affordable quality assured generics. * Countries where ATV is patented, with patents expiring in late 2018 / early 2019

MPP LICENCES GEOGRAPHICAL COVERAGE Product(s) Licensed LIC LMIC UMIC HIC Undefined Total Abacavir (paed.) 31 53 5 1 121 + Atazanavir 52 32 3 122 + Cobicistat 30 42 18 9 4 103 Daclatasvir 46 2 112 + Dolutegravir (paed.) Dolutegravir 6 92 + Elvitegravir 17 8 100 Lopinavir/Ritonavir (paed.) 50 19 102 Lopinavir/Ritonavir (Africa) 26 10 57 + Raltegravir (paed.) 92 Ravidasvir * - 19 + Sutezolid (global) 56 78 218 TDF 23 112 TAF So here is the new geographical scope in view of this announcement Now, the focus of this event is primarily in relation to the new ARVs. So let’s have a look at those. I believe we have today one of the best opportunities we have had so far to transition to new ARVs that can potentially make a significant difference in treatment outcomes. Drugs like dolutegravir not only appear to have important clinical advantages, but also have the potential for being more affordable. Since the scale-up in HIV treatment began in LMICs in the early 2000s, this is one of those rare moments in which we have such an opportunity. An earlier opportunity some years back was with the introduction of TDF, and attempts to phase out d4T.

The Case of Tenofovir (TDF) 10-11 Years from Approval to Scale-up IN THE PAST LONG DELAYS FOR UPTAKE OF NEW MEDICINES IN LOW AND MIDDLE INCOME COUNTRIES The Case of Tenofovir (TDF) Volumes 10-11 Years from Approval to Scale-up This slide, which I have adapted from the Global Fund, shows the transition and uptake of TDF. It took approximately 11 years to see uptake for tenofovir to take off in low and middle income countries, following its approval in the United States. There are a large number of reasons for that across the whole chain of events that need to happen to see a new HIV medicine accessed by those who may need the medicine. These relate to: changes to treatment recommendations, price, availability of suitable formulations including FDCs, inclusion in procurement lists or essential medicines lists, regulatory approval and in-country registration, demand, forecasts, procurement and supply chain issues, understanding on whether the is drug appropriate for different populations (e.g. people with TB, pregnant women), community acceptance, etc. 11 years. This would mean that for a new drug like DTG (approved in August 2013) we would need to wait until 2024 before we started seeing uptake in LMICs But let’s zoom in on one of these, which is the availability of affordable versions of the medicine for use in LMICs Approval of Tenofovir in US Scale-up of Tenofovir in Low and Middle Income Countries Source: GF PPM/PQR data

ACCELERATING AVAILABLITY OF QUALITY ASSURED GENERICS HISTORICAL TIMELINES FROM APPROVAL TO GENERIC COMPETITION Lopinavir/ritonavir: 8 years 5 months Tenofovir disoproxil fumarate: 7 years and 6 months NEW TIMELINES (WITH THE MEDICINES PATENT POOL)* Dolutegravir: ~ 4 years This slide shows the time from approval of a new ARV in developing countries, to the availability of at least 2 quality-assured generic manufacturers for that ARV We see from the slide that with dolutegravir, and soon with TAF (or rather with TAF/FTC), this timeline is being reduced significantly, almost to half. This is a significant reduction. Now, we know that there are many other things that need to fall in place, and I believe that one of the objectives of this event is to begin to unpack how all the different parts of that puzzle. In order to accelerate the process, we need to ensure that things happen in parallel, rather than sequentially. And this already seems to be happening. So while the generic approvals are happening for DTG, studies on use in pregnant women and TB are ongoing, experience in using the medicines in a real-life setting is beginning to accumulate, guidelines are being adapted, support on how to undertake a smooth transition is being issued, etc. TAF/FTC : ~ 3 years 2000 2005 2010 2015 2018 Estimates based on current information. May change depending on changes in development timelines, WHO recommendations, market forecasts and time taken for regulatory review.

MPP DOLUTEGRAVIR LICENCE: OVERVIEW Product: Adult and paediatric formulations of dolutegravir Fixed Dose Combinations: right to make ABC/3TC/DTG and to make other WHO-recommended combinations Geographical Scope: Adult: 92 countries (all LICs, LMICs and SSA); Paediatric: 121 countries. Quality assurance: requires approval by WHO PQ, Stringent Regulatory Authority or Expert Review Panel Royalties: Royalty free in SSA and LICs, 5-10% in countries with patents Other provisions: no restriction to sell outside licence where no patents being infringed So what are some of the main elements of the MPP licences on these products? Here you see an overview. Adult and paediatric formulations of DTG Right to make combinations Geographical scope

MPP TAF LICENCE: OVERVIEW Product: Adult and paediatric formulations of tenofovir alafenamide (TAF) Fixed Dose Combinations: right to make TAF/FTC/EVG/COB and other suitable combinations with TAF Geographical Scope: list of 112 low and middle income countries Manufacturing: licence for manufacturers in India, China and South Africa Quality assurance: requires approval by WHO PQ, US FDA or EMA Royalties: 5% of net sales. No royalties on API. Other provisions: Includes one-time technology transfer

MPP-WHO FORECASTS ON USE OF DOLUTEGRAVIR So are these medicines that important? What is the expected uptake? What you see here is the forecast developed by the MPP in partnership with the WHO, showing us what may happen and how some of these medicines will likely become central to HIV treatment in the not-so-distant future. Of course there are many assumptions behind these graphs. And much will depend on whether we manage to shorten the timelines. If we can accelerate in-country registrations, if data confirms that drugs are safe in pregnant women and people with TB, etc, etc. Source: MPP-WHO, Forecasted demand for Current and New ARV medicines in low and middle income countries, 2016-2026. For overview of assumptions, see: http://www.medicinespatentpool.org/wp-content/uploads/WHO-MPP-Forecasts-Mar-2017.pdf Updated from Gupta et al (2016), Projected Uptake of New Antiretroviral (ARV) Medicines in Adults in Low- and Middle-Income Countries: A Forecast Analysis 2015-2025, PLOS One

MPP-WHO FORECASTS ON USE OF TAF Here is a similar analysis for TAF and here too, you can see the detailed assumptions in the link provided below. Source: MPP-WHO, Forecasted demand for Current and New ARV medicines in low and middle income countries, 2016-2026. For overview of assumptions, see: http://www.medicinespatentpool.org/wp-content/uploads/WHO-MPP-Forecasts-Mar-2017.pdf Updated from Gupta et al (2016), Projected Uptake of New Antiretroviral (ARV) Medicines in Adults in Low- and Middle-Income Countries: A Forecast Analysis 2015-2025, PLOS One

TIMELINES FOR REGULATORY FILING OF PRODUCTS BY MPP GENERIC PARTNERS IN 2017-2018 Dolutegravir based treatments

TIMELINES FOR REGULATORY FILING OF PRODUCTS BY MPP GENERIC PARTNERS IN 2017-2018 Paediatric formulations

TIMELINES FOR REGULATORY FILING OF PRODUCTS BY MPP GENERIC PARTNERS IN 2017-2018 HERE ARE SOME OF THE HCV MEDICINES

TIMELINES FOR REGULATORY FILING OF PRODUCTS BY MPP GENERIC PARTNERS IN 2017-2018 Treatments with TAF

A LOOK INTO THE FUTURE: IN-LICENSING PRIORITIES FOR THE MPP ARV Characteristics Bictegravir Integrase Inhibitor; submitted for regulatory approval Cabotegravir LAI Integrase inhibitor; long acting injectable being studied for treatment and PrEP (Phase 3) Doravirine NNRTi with less common adverse events as compared to efavirenz (Phase 3) Fostemsavir First in class attachment inhibitor; potential role in salvage therapy (Phase 3) Rilpivirine LAI NNRTi, long acting injectable being studied for treatment and PrEP Source: Prioritization of HIV and Hepatitis C medicines for in-licensing by the Medicines Patent Pool (2017)

THANK YOU !! www.medspal.org @medspatentpool www.medicinespatentpool.org www.medspal.org @medspatentpool Thank you to colleagues that have contributed slides to this presentation, in particular Aastha Gupta and Sandeep Juneja. And a strong thank you to all our partners, in government, civil society, communities, originator and generic industry and international organizations. And finally, a thank you to Unitaid who has funded our work and remains our most strategic partner.