Transcript Microbicide Development What are Microbicides?

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
Eastern Europe
Western &
Central Europe & Central Asia
820 000 1.4 million East Asia
1.5 million Middle East & North Africa
770 000
Caribbean
South & South-East Asia
460 000
240 000
Sub-Saharan Africa
4.1 million
Latin America
Oceania
22.5 million
1.4 million
57 000
North America
Total: 33.3 million
UNAIDS/WHO 2010
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
1981
1987
2003
1997
1983
First AIDS
case reported
in the US
ARV “one
drug”
monotherapy
approved for
use
HIV virus
identified
2006
2002
Three-drug
therapy:
HAART.
Drug combinations/
reducing pill burden
30+ approved drugs
for treatment:
research continues
Global
Fund
established
2010
PEPFAR
launched
ARVs in gel
and pill
effective for
HIV prevention
Current and Potential HIV/AIDS Interventions
Prevention
Prevention
 Non-ARV:
 Behavior change
 Male and female
condoms
 STI treatment
 Male circumcision
 HIV vaccines
Treatment
and Care
 ARV-based:
 Prevention of mother
to child transmission
 Post-exposure
prophylaxis (PEP)
 Pre-exposure
prophylaxis (PrEP)
 Microbicides
 ARV treatment
 Treatment for
opportunistic
infections
 Basic care
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:
Vaginal gel
applicator
Long-acting
vaginal ring
Vaginal tablet, soft gel
capsule, film
 Ideally safe, effective, low cost, user friendly
Microbicide Development Process
Research &
Development
Capacity
Building
Clinical
 Trials
Regulatory
Approval
Launch &
Access
• Intellectual
• Research center staff,
• Safety
• Clinical trials
• Manufacturing
property rights
infrastructure, training
• Efficacy
• Licensure
• Service delivery
• Formulations
• Community engagement
• Acceptability
• Post-licensure
• Availability
• Preclinical studies
• HIV incidence studies
studies
 Drug development approach consistent with regulatory path
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
Compound
Dapivirine
DS001 (L-860,167)
DS004 (L-860,872)
DS005 (L-860,882)
DS003 (BMS-599793)
Mechanism of Action
License
Year
Tibotec
2004 Reverse transcription: Stops virus from
copying its genetic material inside human cells
Merck
BMS
Tenofovir
2005 Cell Attachment: Prevents virus from attaching
to human cells
2005 Cell Attachment
2006 Reverse transcription
(IPM & CONRAD)
Gilead
Maraviroc
Pfizer
2008 Cell Attachment
DS007 (L-000889644)
Merck
2008 Cell Fusion: Prevents virus from entering
human cells
Non-exclusive, royalty-free licenses to develop, manufacture and
distribute compounds as microbicides in developing countries
Microbicides in Product Development
Free virus
Attachment
L’644 peptide
Fusion
Tenofovir
Dapivirine
MIV-150
MIV-170
Maraviroc
BMS 793
L167, L872, L882
Pyrimidinediones
Reverse
Transcription
Integration
Protein synthesis
and assembly
Budding
Maturation
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
Private sector
Local
communities
Civil society

Governments
IPM
Pharma
Developers,
Researchers
Research
Centers
Regulatory bodies
IPM’s Research Studies Across the Globe
Clinical Research Centers in Africa
Be
Part
Yoluntu
Centre
More than 10 local partners in 6 countries
conduct research studies on behalf of IPM
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
Site selection & renovation
Staff selection & training
HIV incidence study completed
Microbicide ring & gel trials ongoing
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
Access
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
 Interest 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
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!