THE MEDICINES PATENT POOL Accelerating Access To Quality Assured Generics Through Licensing Of New HCV Medicines Erika Duenas May 2016

THE MEDICINES PATENT POOL Created in 2010 to increase access to quality, appropriate medicines for people living with HIV in developing countries Works by addressing a key challenge in HIV medicines access: patent sharing Expanded to HCV and TB in late 2015 Founded at the request of the international community through the innovative funding mechanism Endorsed by WHO, the UN High Level Meeting on AIDS in 2011 as a promising and innovative public health approach.

PATENT HOLDERS Licences Sub- Licences Medicines GENERIC MANUFACTURERS PEOPLE NEEDING ACCESS TO MEDICINES IN DEVELOPING COUNTRIES ROYALTIES THE MPP MODEL

PROMOTING THE DEVELOPMENT OF FIXED DOSE COMBINATIONS THROUGH LICENSING  Generic by A Generic by B Patented by C Patents on a full HIV treatment can be held by different patent holders making it difficult to develop a pill that brings together various active ingredients Licensing can be a way to address this challenge by pooling all patents needed for developing more affordable combination pills Some combinations are also protected by patents Patented, but licensed to MPP Generic B Generic A

EXPERIENCE IN HIV IN SPEEDING UP DEVELOPMENT Time from originator approval to two quality assured generics

Product(s) Licensed LICLMICUMICHICUndefinedTotal Abacavir (paediatric) Atazanavir Cobicistat Daclatasvir Dolutegravir (paediatric) Dolutegravir Elvitegravir Lopinavir/Ritonavi r (paediatric) Lopinavir/Ritonavi r (Africa) Raltegravir (paediatric) Tenofovir disoproxil fumarate Tenofovir alafenamide MPP LICENCES GEOGRAPHICAL COVERAGE

KEY FEATURES OF MPP LICENCES Non-exclusive, non-restrictive to encourage competition Transparent – all licences are public Wide geographical scope 55% to 80% of middle income countries covered Waivers for regulatory data exclusivity Tiered royalties where possible to enhance coverage Public-Private Market Segmentation to increase geographical scope

KEY FEATURES OF MPP LICENCES Compatibility with TRIPS flexibilities Address diversion and pharmacovigilance Company patent information disclosed Flexibility to create fixed-dose combinations Freedom to challenge patents Out-licensing management Sales allowed outside agreed territory if no patent infringement

7 patent holders with signed agreements 117 countries receiving first-line ARVs from MPP generic partners Over 50 development projects ongoing to accelerate access to new formulations 12 antiretrovirals (ARVs) licensed to the MPP MPP PROGRESS TO DATE 12 generic manufacturers working with the MPP

Atazanavir Daclatasvir (HCV) IN-LICENSING: CONCLUDED AGREEMENTS Lopinavir Ritonavir (separate paediatrics and adults licences) Cobicistat Elvitegravir Emtricitabine Tenofovir Alafenamide Tenofovir Disoproxil Darunavir related Valganciclovir (pricing agreement) Solid dispersion nano technology for HIV Darunavir (paed) (non- assert) Raltegravir (paed) Abacavir (paed) Dolutegravir (paed) Dolutegravir (adults)

GENERIC INDUSTRY PARTNERS MPP is currently running more than 50 development projects with 12 development partners

GENERIC INDUSTRY PARTNERS MPP is currently running more than 50 development projects with 12 development partners WORK IN HEPATITIS C

OUR WORK IN THE HEPATITIS C FIELD million people globally estimated to have the chronic hepatitis C infection Approximately 500’000 people die each year of hepatitis C-related diseases At least 95% of people infected with HCV worldwide are not receiving treatment 1 direct-acting antiviral (DAA) licensed to the MPP 112 low- and middle-income countries covered by the MPP licence 4 MPP’s generic partners to produce and sell daclatasvir

84-85% OF THE TOTAL HCV INFECTIONS ARE IN LICS OR MICS WITH HETEROGENEOUS GENOTYPE DISTRIBUTIONS Sources: Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014 Nov;61(1S):S45-S57. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011 Feb;17(2): HCV RNA+ InfectionsHCV Genotype Distribution 15-16% 23-29% 43-49% 12-13% LIC – Low Income Countries MIC – Middle Income Countries including upper middle and lower middle

THE PATENT ON MOST NEW HCV MEDICINES WILL NOT EXPIRE UNTIL THE MID-2020S Hepatitis C Medicines – Technology and Market Landscape. UNITAID 2015 Report. Patent situation of key products for treatment of hepatitis C. ABT-450, Daclatasvir, Dasabuvir, Ledipasvir, Ombitasvir, Simeprevir, and Sofosbuvir. Working papers. Geneva: World Health Organization; 2014

OVERVIEW OF NEW DIRECTLY ACTING ANTIVIRALS Phase I Phase II Phase III FDA Approved (Any genotype) Paritaprevir/r (ABT-450/r) NS3/4A inhibitor AbbVie Paritaprevir/r (ABT-450/r) NS3/4A inhibitor AbbVie Sofosbuvir (GS-7977/PSI-7977) NS5B inhibitor – nuc 3 Gilead Sofosbuvir (GS-7977/PSI-7977) NS5B inhibitor – nuc 3 Gilead ABT NS3/4A inhibitor AbbVie ABT NS3/4A inhibitor AbbVie Daclatasvir (BMS ) NS5A inhibitor BMS Daclatasvir (BMS ) NS5A inhibitor BMS ABT-530 NS5A inhibitor AbbVie ABT-530 NS5A inhibitor AbbVie Dasabuvir 11 (ABT-333) NS5B inhibitor – non- nuc AbbVie Dasabuvir 11 (ABT-333) NS5B inhibitor – non- nuc AbbVie Asunaprevir 4 (BMS ) NS3/4A inhibitor BMS Asunaprevir 4 (BMS ) NS3/4A inhibitor BMS Ombitasvir (ABT-267) NS5A inhibitor AbbVie Ombitasvir (ABT-267) NS5A inhibitor AbbVie Beclabuvir (BMS ) NS5B inhibitor – non- nuc BMS Beclabuvir (BMS ) NS5B inhibitor – non- nuc BMS Vedroprevir (GS-9451) NS3/4A inhibitor Gilead Vedroprevir (GS-9451) NS3/4A inhibitor Gilead GS-9857 NS3/4A inhibitor Gilead GS-9857 NS3/4A inhibitor Gilead Ledipasvir (GS-5885) NS5A inhibitor Gilead Ledipasvir (GS-5885) NS5A inhibitor Gilead Velpatasvir (GS-5816) NS5A inhibitor Gilead Velpatasvir (GS-5816) NS5A inhibitor Gilead Simeprevir (TMC435) NS3/4A inhibitor Janssen Simeprevir (TMC435) NS3/4A inhibitor Janssen GSK / JNJ NS5A inhibitor GSK  Janssen GSK / JNJ NS5A inhibitor GSK  Janssen Odalasvir (ACH-3102) NS5A inhibitor Achillion  Janssen Odalasvir (ACH-3102) NS5A inhibitor Achillion  Janssen ACH-3422 NS5B inhibitor – nuc Achillion  Janssen ACH-3422 NS5B inhibitor – nuc Achillion  Janssen Boceprevir (SCH ) NS3/4A inhibitor Merck Boceprevir (SCH ) NS3/4A inhibitor Merck Vaniprevir 5 (MK-7009) NS3/4A inhibitor Merck Vaniprevir 5 (MK-7009) NS3/4A inhibitor Merck Grazoprevir (MK-5172) NS3/4A inhibitor Merck Grazoprevir (MK-5172) NS3/4A inhibitor Merck Elbasvir (MK-8742) NS5A inhibitor Merck Elbasvir (MK-8742) NS5A inhibitor Merck MK-8408 NS5A inhibitor Merck MK-8408 NS5A inhibitor Merck Samatasvir (IDX719) NS5A inhibitor Merck Samatasvir (IDX719) NS5A inhibitor Merck MK-3682 / IDX21437 NS5B inhibitor – nuc Merck MK-3682 / IDX21437 NS5B inhibitor – nuc Merck MK-7680 Class unknown Merck MK-7680 Class unknown Merck Ravidasvir 6 (PPI-668; ASC16) NS5A inhibitor Presidio  Pharco; Ascletis Ravidasvir 6 (PPI-668; ASC16) NS5A inhibitor Presidio  Pharco; Ascletis PPI-383 NS5B inhibitor – non- nuc Presidio PPI-383 NS5B inhibitor – non- nuc Presidio Setrobuvir (ANA-598, RG7790) NS5B inhibitor – non- nuc Anadys  Roche Setrobuvir (ANA-598, RG7790) NS5B inhibitor – non- nuc Anadys  Roche Mericitabine NS5B inhibitor – nuc Roche Mericitabine NS5B inhibitor – nuc Roche Danoprevir/r 7 (ITMN-191, ASC08) NS3/4A inhibitor Roche; Ascletis Danoprevir/r 7 (ITMN-191, ASC08) NS3/4A inhibitor Roche; Ascletis TD-6450 NS5A inhibitor Theravance  TREKtx TD-6450 NS5A inhibitor Theravance  TREKtx Lomibuvir (VX-222) NS5B inhibitor – non- nuc Vertex Lomibuvir (VX-222) NS5B inhibitor – non- nuc Vertex VX NS5B inhibitor – nuc Alios  Vertex VX NS5B inhibitor – nuc Alios  Vertex Telaprevir (VX-950) NS3/4A inhibitor Vertex  Janssen Telaprevir (VX-950) NS3/4A inhibitor Vertex  Janssen EDP-239 NS5A inhibitor Enanta EDP-239 NS5A inhibitor Enanta IDX21459 / MK-1075 ? NS5B inhibitor – nuc Merck IDX21459 / MK-1075 ? NS5B inhibitor – nuc Merck AL-335 NS5B inhibitor – nuc Alios / Janssen AL-335 NS5B inhibitor – nuc Alios / Janssen Faldaprevir 10 (BI ) NS3/4A inhibitor BI  TREKtx Faldaprevir 10 (BI ) NS3/4A inhibitor BI  TREKtx GSK Oral [& LAI] NS5B inhibitor – non- nuc GSK GSK Oral [& LAI] NS5B inhibitor – non- nuc GSK AL-704 NS5B inhibitor – nuc Alios / Janssen AL-704 NS5B inhibitor – nuc Alios / Janssen Furaprevir 13 (TG-2349) NS3/4A inhibitor TaiGen Furaprevir 13 (TG-2349) NS3/4A inhibitor TaiGen MK-2248 Class unknown Merck MK-2248 Class unknown Merck MB-110 NS5A inhibitor Microbio Co. MB-110 NS5A inhibitor Microbio Co. MK NS3/4A Merck MK NS3/4A Merck Sovaprevir (ACH-1625) NS3/4A inhibitor Achillion  Janssen Sovaprevir (ACH-1625) NS3/4A inhibitor Achillion  Janssen

Year-long process to explore feasibility of entering HCV field MPP would focus on pan-genotypic regimens as these are best suited for resources limited settings Our aim would be to reduce pricing of the new therapies through expanded voluntary licensing programs and convince companies to follow a licensing route MPP hepatitis C licensing would seek to: Apply the public health terms and conditions established in HIV licenses to the HCV licenses Be complementary to other access options Seek wider geographical coverage MPP will also encourage speed to market of quality approved generics through its Sub-licensing management program and work with partners to encourage appropriate pan-genotypic treatments MPP FOCUS AND ADDED VALUE IN HCV

MPP LICENCE ON DACLATASVIR In November 2015, the MPP obtained its first licence on an HCV medicine The licence is on daclatasvir a new oral DAA already included in the WHO Model List of Essential Medicines Key features of the licence: Enables manufacturing of the product by generic manufacturers based anywhere in the world For the supply of at least 112 countries (including 80 middle-income countries) Other countries in which no patents on DCV may also be able to procure from MPP licensees Royalty-free: no royalties flowing back to BMS Licensees can combine DCV with other medicines to create FDCs Licensees need to meet strict quality assurance requirements Text of licence public – available on MPP website

On day of announcement, MPP issued Expression of Interest calling on generic manufacturers interested in getting a licence First four licences have been issued to: Cipla, Emcure, Hetero and Natco Several other requests for licences are being reviewed and second wave of licensees to be announced shortly Licensees expecting to file for approval with the WHO Prequalification towards end of this year GENERIC MANUFACTURING

LIST OF COUNTRIES INCLUDED IN LICENCE

THANK YOU

Geneva, 25 April 2016: The MPP and ViiV Healthcare signed an extension of their current licensing agreement today to increase access to dolutegravir (DTG), a promising new antiretroviral, to cover all remaining lower middle-income countries. Armenia, Moldova, Morocco and Ukraine MPP sub-licensees can now sell in countries that are home to 94% of people living with HIV in the developing world. EXPANSION OF THE SCOPE FOR DGT