International Partnership for Microbicides New Science, New Hope: Giving Women Power Over AIDS The John Kevany Memorial Lecture Zeda Rosenberg, ScD, Chief Executive Officer NUI Maynooth, 29 November 2010

The Challenge of HIV/AIDS

People Living with HIV in 2009 Total: 33.3 million UNAIDS/WHO 2010 Western & Central Europe Middle East & North Africa Sub-Saharan Africa 22.5 million Eastern Europe & Central Asia 1.4 million South & South-East Asia 4.1 million Oceania North America 1.5 million Latin America 1.4 million East Asia Caribbean

Women’s Vulnerability to HIV Biological, economic and socio-cultural factors: Male-to-female transmission higher Young women at even greater risk Financial dependence on male partners Inequality of women (exploitation and violence) Cultural practices such as early marriages, intergenerational sex and concurrent partnerships

The Face of HIV/AIDS in Africa Female  60% in sub-Saharan Africa Young  3-5 times more likely to become infected Married and monogamous  Stable relationships not a haven A mother  Pregnancy complicated by HIV World Bank Photo

HIV Prevention – The Global Response

From AIDS Treatment to HIV Prevention First AIDS case reported in the US HIV virus identified ARV “one drug” mono- therapy approved for use Three-drug therapy: HAART. 30+ approved drugs for treatment: research continues 2002 Global Fund established 2003 Drug combinations/ reducing pill burden ARVs in gel and pill effective for HIV prevention PEPFAR launched

Prevention  Behavior change  Male and female condoms  STI treatment  Male circumcision  HIV vaccines  Prevention of mother to child transmission  Post-exposure prophylaxis (PEP)  Pre-exposure prophylaxis (PrEP)  Microbicides  ARV treatment  Treatment for opportunistic infections  Basic care Current and Potential HIV/AIDS Interventions Treatment and Care Prevention ARV-based: Non-ARV:

Promise of ARV-Based PrEP Proof-of-concept for Truvada® Appropriate for men and women Uses approved ARV drugs Convenient dosing: oral Potential for different dosing strategies Intermittent dosing Monthly injection Can combine more than one ARV in a single product

iPrEx: First Proof-of-Concept for PrEP First efficacy trial of ARV-based pre-exposure prophylaxis (PrEP) for HIV prevention Phase III: daily oral Truvada® Two ARV drugs in one tablet: TDF and FTC 2,499 MSM at 11 sites in Brazil, Ecuador, Peru, South Africa, Thailand and the U.S. First PrEP “proof-of-concept” 44% protection against HIV 73% protection in volunteers who took study medication 90% or more of days Safe, well-tolerated as tested PrEP trials in other populations underway

Promise of ARV-based Microbicides Antiretroviral (ARV)-based microbicides:  Target HIV specifically  Based on the same types of drugs successfully used to treat HIV and prevent mother to child transmission  Can be delivered in a variety of user-friendly forms: vaginal gel, ring, film, others  Potential to be developed as combination products Proof of concept: tenofovir gel

CAPRISA 004 Trial First efficacy trial of an ARV-based microbicide Tenofovir gel (results July 2010) First microbicide trial to show “proof of concept” 889 women in South Africa Gel used within 12 hours before and after sex 39% protection against HIV 51% protection against HSV-2 Gel safe as tested & no drug resistance detected VOICE trial ongoing; additional study(ies) planned to start in 2011

Microbicide Development

What are Microbicides? Topical products used to prevent HIV transmission to women Could be delivered in many forms: Ideally safe, effective, low cost, user friendly Vaginal gel applicator Long-acting vaginal ring Vaginal tablet, soft gel capsule, film

Microbicide Development Process Research center staff, infrastructure, training Community engagement HIV incidence studies Safety Efficacy Acceptability Clinical trials Licensure Post-licensure studies Manufacturing Service delivery Availability  Drug development approach consistent with regulatory path Intellectual property rights Formulations Preclinical studies

IPM’s Mission Nonprofit product development partnership (PDP) Offices in the United States, South Africa, Europe IPM’s mission is to prevent HIV transmission by supporting the development and availability of safe and effective microbicides and other HIV prevention tools for use by women in developing countries

Partnerships With Industry Non-exclusive, royalty-free licenses to develop, manufacture and distribute compounds as microbicides in developing countries CompoundLicenseYear Mechanism of Action DapivirineTibotec2004 Reverse transcription: Stops virus from copying its genetic material inside human cells DS001 (L-860,167) DS004 (L-860,872) DS005 (L-860,882) Merck 2005Cell Attachment: Prevents virus from attaching to human cells DS003 (BMS )BMS2005Cell Attachment Tenofovir (IPM & CONRAD) Gilead 2006Reverse transcription MaravirocPfizer2008Cell Attachment DS007 (L )Merck2008Cell Fusion: Prevents virus from entering human cells

Microbicides in Product Development Free virus Attachment Fusion Reverse Transcription Protein synthesis and assembly Budding Maturation Integration Maraviroc BMS 793 L167, L872, L882 Tenofovir Dapivirine MIV-150 MIV-170 Pyrimidinediones L’644 peptide

Need for Multiple Products & Formulations Different women, different preferences More product choices, more options for protection Impact of adherence on efficacy - product won’t help if women don’t use it Male partners’ opinions and preferences important

Vaginal Rings: An Attractive Technology Long-acting Easy to use Flexible ring, can be self-inserted Suitable for developing world Heat-stable Used safely for other purposes Contraceptive and hormone therapy rings Suitable for drug combinations Dapivirine ring Phase III planned in 2011

IPM Partnerships Multilaterals Local communities Private sector Governments Pharma Civil society Research Centers Developers, Researchers Regulatory bodies IPM

IPM’s Research Studies Across the Globe

Clinical Research Centers in Africa More than 10 local partners in 6 countries conduct research studies on behalf of IPM Be Part Yoluntu Centre

Capacity Building at Research Centers Community engagement Referral networks for medical care, treatment, support Infrastructure and equipment Staff training and development Communications, messaging, tools Financial management support HIV incidence studies

Projet Ubuzima, Kigali, Rwanda HIV incidence studies and microbicide gel trial completed Microbicide gel trial ongoing Microbicide ring trial planned

Ladysmith, KwaZulu-Natal, South Africa HIV incidence study completed Microbicide ring & gel trials ongoing Site selection & renovation Staff selection & training

Benefiting People, Communities, Countries Promote reproductive health and HIV awareness Empower women through education and counselling Involve men in HIV prevention Encourage HIV testing Strengthen delivery of and access to health services Engage communities, build community advisory (CAB) Provide employment and professional development Building medical research capabilities in geographical areas of need

AccessAccess

Access Principles: Planning for Success Availability Accessibility Acceptability Affordability

Acceptability Studies in Africa Vaginal ring, film, tablet, soft gel capsule All formulations acceptable Different formulations preferred in different countries Women very likely to use all products to prevent HIV I nterest in discreet use

Access: Preparing for Success IPM Access Strategy Intellectual property agreements evolution Pfizer, Merck 2008, Tibotec Acceptability/market research studies IPM 011, PAS 2 Global manufacturing survey completed LSHTM modeling of microbicide introduction Pharma lessons learned ARV treatment intro Annual Microbicide Access Forum

Key Regulatory Aspects of Access Demonstration of efficacy in Phase III trial does not automatically translate into product licensure or immediate access to product Regulatory licensure requires review for: Product quality (CMC) Safety (preclinical and clinical) Efficacy However, very limited access to product can be achieved through clinical programs

Empowering Women Empowering Women

Women’s Right to Health Human right to health in many UN rights treaties Women’s right to health in ICPD Programme of Action (1994) The Beijing Platform for Action (1995) Women’s productivity and humanity undermined without high standard of health HIV protection responds to woman’s risks of infection Microbicides could provide a vital HIV prevention tool for women and enable them to protect their health and that of their families

Microbicides and the Millennium Development Goals Microbicides have the potential to impact 7 of 8 MDGs Source: United Nations

Concluding Remarks

Ireland – Pioneering Support IPM thanks the people of Ireland and the Irish Government and for your unwavering commitment to microbicide development and the needs of women in the developing world.

Women Urgently Need Microbicides “A microbicide could mean the difference between life and death for millions of women. Let us do everything in our power to accelerate its development.” Mrs. Graça Machel

THANK YOU!