Public health, innovation and intellectual property 1 |1 | Innovation and Access to Medicines: Case Study for HIV/AIDS and Hepatitis C Trends in voluntary licensing December 5, 2014 Dr. Peter Beyer Innovation and Access to Medicines: Case Study for HIV/AIDS and Hepatitis C Trends in voluntary licensing December 5, 2014 Dr. Peter Beyer

2001: Pharma companies sue South African Government over parallel imports - no voluntary license agreements 2001: WTO-Doha Declaration; stavudine case in South Africa (Yale - BMS - Aspen) 2002: Creation of Global Fund to Fight AIDS, Tuberculosis & Malaria 2003: Decision of South African Competition Authority with respect to ARVs: settlement involving license agreements with generic manufacturers : Compulsory licenses in Brazil, Ecuador, Ghana, India, Indonesia, Malaysia, Mozambique, Thailand, Zambia, Zimbabwe 2008: Adoption WHO Global Strategy & Action Plan on PH, innovation and IP 2010: Creation of the Medicines Patent Pool 2013: 7 out of 8 originator companies with HIV products in the market have license/immunity-from-suit agreements 2014: first agreements on new hepatitis C treatments

Voluntary license agreements & non-assert declarations: HIV adults INN LicensorYearScopeNo countriesLicsees EFVMSD2007South Africa1 (allows export to SSA)Several d4TBMS2001SSA, India. country list50Several DDLBMS2006SSA; India; country list50Several RALMSD2011LIC; SSA562 SQVRoche2006LDC; SSA65Several DRVTibotec (Janssen/J&J)2012 Non-assert: LDC; SSA License: India 65 1+non- assert. ZDV; ZDV/3TCViiV Healthcare2010LDC; LIC; SSA69Several TPVBoehringer-Ingelheim2004/07LIC; LDC; Africa, India78Several NVPBoehringer-Ingelheim2004/07LIC; LDC; Africa; India78Several DTG; DTG/ABCMPP: ViiV Healthcare2014Country list73 (+ no patent count.)MPP EVG; QUAD TDF+FTC+EVG MPP: Gilead Sciences2011Country list100Several EVG; QUAD TDF+FTC+EVG Gilead Sciences2011Country list semi-exclusive licenses for MICs 4 ATVMPP: BMS2013Country list110 (+ 34 no patent count.)MPP RPV/TDF/3TC or FTC; RPV Tibotec (Janssen/J&J)2011Country list1125 TDFGilead Sciences2006/11Country list112Several TDF; TAF; FTCMPP: Gilead Sciences2011/14Country list112Several

Public health, innovation and intellectual property 4 |4 | Trends & Challenges Geographical scope: Companies expanded products & territory over time since 2010 pushed by MPP; most agreements include SSA, LDCs and/or LICs (= 68 countries) + certain number of MICs Challenge: (upper) middle-income (except those in SSA) Compulsory licenses: shipment allowed under MPP licenses to countries that issue compulsory licenses Non-patent territory: included in some licenses (MPP) Transparency: very limited information available on individual agreements; MPP agreements published

Public health, innovation and intellectual property 5 |5 | Countries with greatest no. of HCV infections Adapted from Gower E et al. J Hepatol (2014)

Public health, innovation and intellectual property 6 |6 | Hepatitis C Agreements signed on sofosbuvir –Draft publicly available, incl. patent data –91 countries = around half of total number of middle-income countries –Allows shipment under compulsory licenses –Shipments to non-patent territories prohibited (text unclear) –Limited to Indian producers (including API) –Allows combinations with "foreign" products (e.g. daclatasvir) Agreements announced for daclatasvir: 90 countr ies

What is WHO doing?

Public health, innovation and intellectual property 8 |8 | WHO’s role in improving access AwarenessTestingReferral Disease- stage assessment TreatmentMonitoring World Hepatitis Day Assistance with national planning Improved prevalence estimates Prequalification of diagnostics Screening/ testing guidelines Treatment Guidelines Prequalification of medicines Essential Medicines List Price Reporting Mechanism Advocacy, guidance and technical assistance for improved treatment access ScreeningCareTreatment Prevention, including Injection safety Hospital infections Safe blood products Needle sharing programmes

Public health, innovation and intellectual property 9 |9 | Recommendations 1. HCV Ab testing offered to individuals part of population with high HCV prevalence or history of HCV-risk exposure / behaviour 2. RNA testing following positive HCV Ab test to establish diagnosis of active infection and for treatment evaluation 3. Alcohol-intake assessment + offer of behavioural alcohol reduction intervention for persons with moderate-high alcohol intake 4. Use non-invasive tests (APRI or FIB4) for assessment of liver fibrosis 5.Assessment of all adults and children with chronic HCV, including PWID for antiviral treatment 6. PEG-IFN + Ribavirin rather than standard non PEG-IFN + Ribavirin 7. Telaprevir or boceprevir in genotype 1 infection 8. Sofosbuvir + Ribavirin ± PEG-IFN in genotypes 1, 2, 3 and 4 infection 9. Simeprevir + PEG-IFN + Ribavirin in genotype 1 infection HCV guidelines recommendations (2014)

Public health, innovation and intellectual property 10 | WHO Essential Medicines Lists Satisfy priority health care needs, should be available at all times in appropriate dosage forms, of assured quality at an affordable price Contains more than 400 medicines (18 th EML) Revised every two years: next Expert Committee meeting: April 2015 Everybody can file applications Applications received: –daclatasvir –simeprevir –sofosbuvir –sofosbuvir/ledipasvir FDC

Public health, innovation and intellectual property 11 | UN/WHO Prequalification Vision: Good quality medicines for everyone Call for Expressions of Interest Hepatitis C (2014) –sofosbuvir tablet, 400mg –simeprevir capsule, 150mg –ribavirin capsule, 200mg, 400mg, 600mg

Public health, innovation and intellectual property 12 | Patent landscapes sofosbuvirGilead Sciences dasabuvir (ABT-333)AbbVie ombitasvir (ABT-267)AbbVie daclatasvir (BMS )BMS ledipasvir (GS-5885)Gilead Sciences ABT-450AbbVie simeprevir (TMC435)Janssen

Public health, innovation and intellectual property 13 | Concluding Remarks Increasing number and increasing scope of HIV licenses Important to license early in the life-cycle with broad scope Potential for reduced prices through increased competition if licenses allow for robust competition Part of the solution, but countries outside the agreements have to seek other avenues Hepatitis C: first licenses signed. Will other companies follow? Hepatitis C: What role for the Medicines Patent Pool? Prevention!

Public health, innovation and intellectual property 14 | Promoting Access to Medical Technologies and Innovation edical_innovation/en/ /en/ Dr Peter Beyer Senior Advisor World Health Organization Tel