International Partnership for MicrobicidesInternational Partnership for MicrobicidesInternational Partnership for MicrobicidesInternational Partnership for Microbicides

Advancing HIV-Prevention Options for WomenAdvancing HIV-Prevention Options for Women

Parliamentary Seminar on New HIV-Prevention Parliamentary Seminar on New HIV-Prevention TechnologiesTechnologies

Dr. Zeda Rosenberg

Helsinki, 24 October 2007

The Face of HIV is Increasingly…The Face of HIV is Increasingly…The Face of HIV is Increasingly…The Face of HIV is Increasingly…

FemaleFemale

YoungYoung

Married and monogamousMarried and monogamous

A motherA mother

What is a Microbicide?What is a Microbicide?What is a Microbicide?What is a Microbicide?

Vaginal products to prevent or reduce HIV

Could be delivered in many forms:

Vaginal applicator

Vaginal ring

gel

intravaginal ring

softgel capsule

vaginal film

vaginal tablet

sponge

transmission

Microbicides in Product DevelopmentMicrobicides in Product DevelopmentMicrobicides in Product DevelopmentMicrobicides in Product Development

Free virusLactin-VInvisible Condom

AttachmentFusion

Replication(RT)

Protein synthesis and assembly

Budding

Maturation

Locus small molecules

CarraguardPRO2000SPL7013 (VivaGel)Monoclonal antibodiesDS003 (BMS)DS001 (Merck)DS006 (Maraviroc)SCHs (Schering-Plough)

S-DABODapivirine (TMC120)UC781Tenofovir (PMPA)PC815 (MIV150 + Carraguard)

IPM compounds

IPM-supported compounds

Pyrimidinediones (Samjin)

BufferGel

Integration

Microbicide Development ProcessMicrobicide Development ProcessMicrobicide Development ProcessMicrobicide Development Process

Research & Development

• Pipeline

• Basic research

• Pre-clinical studies

• Lead selection

• Community engagement

• Site selection

• Site preparation

• Site monitoring

• Incidence studies

Site Development Clinical Trials

• Pharmacokinetic

• Safety

• Efficacy

• Acceptability

Regulatory Approval

• Clinical Trials

• Licensure

• Post-licensure

studies

Launch & Access

• Manufacturing

• Service delivery

• Marketing

Early Generation MicrobicidesEarly Generation MicrobicidesEarly Generation MicrobicidesEarly Generation Microbicides

Products that non-specifically block HIV from interacting with target cells

In efficacy trials

Partial, low or no effectiveness

Short-acting (used near time of sex)

Candidate Microbicide

PhaseMechanism

of Action

Sponsor/Developer Trial Location

Carraguard 3 Entry Inhibitor

Gates, USAID /Population Council

South Africa – Cape Town, Durban, Medunsa

PRO 2000 3 Entry Inhibitor

UK Medical Research Council, DFID / MDP

South Africa – Mtubatuba, Durban, JohannesburgUganda – Masaka Tanzania – Mwanza Zambia – Mazabuka

PRO 2000 &Buffer Gel

2/2B Entry Inhibitor &Vaginal Defense Enhancer

NIAID / HPTN (MTN) Zimbabwe – Harare, ChitungwizaZambia – Lusaka Malawi – Blantyre, Lilongwe South Africa – Durban, HlabisaUnited States – Philadelphia

Early Generation Efficacy TrialsEarly Generation Efficacy Trials Early Generation Efficacy TrialsEarly Generation Efficacy Trials

Next Generation MicrobicidesNext Generation MicrobicidesNext Generation MicrobicidesNext Generation Microbicides

Based on antiretroviral drugs used to treat HIV• IPM’s microbicide candidates fall in this category• Highly potent and HIV-specific

Delivery mechanism for sustained protection• Once a day or less• Gels, intravaginal rings, vaginal tablets and others

Developed as single drugs and in combination

Trial of tenofovir gel initiated May 2007• South Africa (CAPRISA, CONRAD, USAID)• Coitally dependent

IPM Mission & DonorsIPM Mission & DonorsIPM Mission & DonorsIPM Mission & Donors

Established in 2002 as a non-profit product development partnership (PDP).

IPM’s mission is to prevent HIV transmission by accelerating the development and availability of safe and effective microbicides for use by women in developing countries.

DonorsBelgium, Canada, Denmark, France, Germany, Ireland,

Norway, Netherlands, Sweden, United Kingdom, United States, European Commission, World Bank, UNFPA, Bill & Melinda Gates Foundation, Rockefeller Foundation

Partnerships with IndustryPartnerships with IndustryPartnerships with IndustryPartnerships with Industry

Year Company Compound Type

2004 Tibotec (J&J) Dapivirine (TMC120) NNRTI

2005 Merck M167, M872, M882 CCR5 blockers

2005 Bristol- Myers Squibb BMS793 gp120 binder

2006 Gilead Tenofovir (PMPA gel) NRTI

Year Company Compound Type

2007 Pfizer Maraviroc CCR5 blocker

2007 Schering-Plough Anti-HIV Compounds CCR5 blockers

IPM Licenses with Industry

IPM Material Transfer Agreements with Industry

GMP Manufacture

Applicator Filling LinePennsylvania, US

Research and DevelopmentResearch and DevelopmentResearch and DevelopmentResearch and Development

IPM Clinical Studies of DapivirineIPM Clinical Studies of DapivirineIPM Clinical Studies of DapivirineIPM Clinical Studies of Dapivirine

2004-05

Safety/Feasibility

2007 2008

PK

Safety

PK/Feasibility

Safety

PK

Safety Male tolerance

Studies in Belgium, Kenya, Rwanda, South Africa, Tanzania

2009

2005-06

Efficacy trial

Seroconverter protocol

PK

IPM Site Development in AfricaIPM Site Development in AfricaIPM Site Development in AfricaIPM Site Development in Africa

Advanced stage site development(cohort incidence studies)

Early stage site development (cross-sectional incidence studies)

Why Test Microbicides in Why Test Microbicides in Developing Countries?Developing Countries?

Why Test Microbicides in Why Test Microbicides in Developing Countries?Developing Countries?

Countries in greatest need of new HIV prevention options

Communities with high HIV incidence

Test microbicides in contexts in which they will be used

Clinical and regulatory implications

Building understanding and support

IPM Research Center PartnersIPM Research Center PartnersIPM Research Center PartnersIPM Research Center Partners

AfrimeAfrimesh sh

ResearResearch and ch and CareCare

LadysmitLadysmith h

Hospice Hospice AssociatiAssociati

onon

Stanza Stanza Bopape Bopape

CommunCommunity Trustity Trust

Community engagement

Informed consent process Counseling

Pre- and post-HIV testing Condom education and provision Family planning

Referrals Those who initially screen HIV-

positive Pregnancy Social harms

Treatment Sexually transmitted infections Adverse reactions Antiretrovirals for HIV infections

Ethical Guidelines for Clinical TrialsEthical Guidelines for Clinical TrialsEthical Guidelines for Clinical TrialsEthical Guidelines for Clinical Trials

Product Acceptability StudiesProduct Acceptability StudiesProduct Acceptability StudiesProduct Acceptability Studies

Placebo gel formulations• Market research in Kenya, Zambia, South Africa

(500 volunteers), 2006• Assess women’s preferences• Supported acceptability of a daily product

Placebo vaginal ring• Study launched February 2007 (200 volunteers)• Four sites in South Africa, Tanzania, Kenya• Collect early safety and acceptability data

Vaginal tablet and film: initiated Q4 2007

IPM Access PrinciplesIPM Access Principles IPM Access PrinciplesIPM Access Principles

Availability

Accessibility

Acceptability

Affordability

Sample Access ActivitiesSample Access Activities Sample Access ActivitiesSample Access Activities

Intellectual property agreements

Community mobilisation for trials

Market research

Mapping regulatory pathways

Surveying manufacturing capacity

Modelling introduction scenarios

Assessing health system capacity

Lessons learned from other health technologies

European ActivitiesEuropean ActivitiesEuropean ActivitiesEuropean Activities

Europrise: European Vaccines & Microbicides Initiative Int’l research network of 33 partners from 10 countries Chair of IPM’s SAB is coordinator & IPM Belgium is affiliate member

EMPRO: European Microbicides Project Int’l research network of 25 partners in Europe & Africa IPM has advisory role & is planning a joint Phase IIVR trial

EDCTP: European and Developing Countries Clinical Trials Partnership

Partnership of 14 EU countries, Norway & Switzerland to develop clinical interventions in cooperation with 18 African countries

IPM provides proposal review and expertise and supports bridge funding for sites, as requested

IPM Support of Global IPM Support of Global Development EffortsDevelopment Efforts

IPM Support of Global IPM Support of Global Development EffortsDevelopment Efforts

Improvement in health

Reduction in new HIV infections Increased community education and mobilization Regulatory path for new prevention technologies

Capacity building

Infrastructure and equipment Income and skills generation (jobs and training) Access to medical care and support

Women’s rights

Contribution to MDGsContribution to MDGsContribution to MDGsContribution to MDGs

“Microbicides are a development priority. I can think of no other technology that has the potential to dramatically improve the health of women in developing countries. Moreover, I do not see how we can meet the MDGs without safe and effective microbicides.”

STEPHEN LEWIS, 2005 Former UN Special Envoy for HIV/AIDS in Africa