International Partnership for MicrobicidesInternational 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 2009People Living with HIV in 2009

Total: 33.3 million UNAIDS/WHO 2010

Western & Central Europe

820 000Middle East & North Africa

460 000Sub-Saharan Africa

22.5 million

Eastern Europe & Central Asia

1.4 million

South & South-East Asia

4.1 millionOceania

57 000

North America

1.5 million

Latin America

1.4 million

East Asia

770 000Caribbean

240 000

Women’s Vulnerability to HIVWomen’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 AfricaThe 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 HIVWorld Bank Photo

HIV Prevention – The Global Response

From AIDS Treatment to HIV PreventionFrom AIDS Treatment to HIV Prevention

1981

1983

19871997

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

20062010

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 InterventionsCurrent and Potential HIV/AIDS Interventions

Treatmentand Care

Prevention

ARV-based:Non-ARV:

Promise of ARV-Based PrEPPromise 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 PrEPiPrEx: 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 MicrobicidesPromise 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 TrialCAPRISA 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?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 ProcessMicrobicide 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

Research &

DevelopmentCapacity Building Clinical

Trials

Regulatory Approval

Launch & Access

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 IndustryPartnerships With Industry

Non-exclusive, royalty-free licenses to develop, manufacture and

distribute compounds as microbicides in developing countries

Compound License Year Mechanism of Action

Dapivirine Tibotec 2004 Reverse transcription: Stops virus from copying its genetic material inside human cells

DS001 (L-860,167)DS004 (L-860,872)DS005 (L-860,882)

Merck2005 Cell Attachment: Prevents virus from attaching

to human cells

DS003 (BMS-599793) BMS 2005 Cell Attachment

Tenofovir(IPM & CONRAD) Gilead

2006 Reverse transcription

Maraviroc Pfizer 2008 Cell Attachment

DS007 (L-000889644) Merck 2008 Cell Fusion: Prevents virus from entering human cells

Microbicides in Product DevelopmentMicrobicides in Product Development

Free virus

Attachment

Fusion

ReverseTranscription

Protein synthesisand assembly

Budding

Maturation

Integration

Maraviroc

BMS 793L167, L872, L882

Tenofovir

Dapivirine

MIV-150

MIV-170

Pyrimidinediones

L’644 peptide

Need for Multiple Products & FormulationsNeed 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 TechnologyVaginal 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 PartnershipsIPM Partnerships

Multilaterals

Local communities

Private sector

Governments

Pharma

Civil society

Research Centers

Developers, Researchers

Regulatory bodies

IPM

IPM’s Research Studies Across the GlobeIPM’s Research Studies Across the Globe

Clinical Research Centers in AfricaClinical 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 CentersCapacity 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, RwandaProjet Ubuzima, Kigali, Rwanda

HIV incidence studies and microbicide gel trial completed

Microbicide gel trial ongoing

Microbicide ring trial planned

Ladysmith, KwaZulu-Natal, South AfricaLadysmith, KwaZulu-Natal, South Africa

HIV incidence study completedMicrobicide ring & gel trials ongoing

Site selection & renovation Staff selection & training

Benefiting People, Communities, CountriesBenefiting 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

Access Access

Access Principles: Planning for SuccessAccess Principles: Planning for Success

Availability

Accessibility

Acceptability

Affordability

Acceptability Studies in AfricaVaginal ring, film, tablet, soft gel capsule

Acceptability Studies in AfricaVaginal 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

Interest in discreet use

Access: Preparing for SuccessAccess: 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 AccessKey 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 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 and the Millennium Development Goals

Microbicides have the potential to impact

7 of 8 MDGs

Source: United Nations

Concluding RemarksConcluding Remarks

Ireland – Pioneering Support 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 MicrobicidesWomen 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!THANK YOU!