topical microbicides antiviral drugs advisory committee august 20, 2003

Topical MicrobicidesTopical Microbicides

Antiviral Drugs Advisory Committee

August 20, 2003


• Definition– Drug or biologic product for the

reduction of transmission of HIV and/or other STIs, applied topically

– Varied formulations, +/- device – With or without spermicidal activity– Vagina or rectum as route of

administration prior to intercourse

Topical Microbicides Topical Microbicides

• Ideal Characteristics– Non-irritating – Discreet

• Odorless• Tasteless• Colorless

– Stable in most environments– Affordable

• Safe and Effective


• Classes of Drugs– Surfactants– Buffering agents– Chemical barriers– Entry inhibitors– Nucleoside and non-nucleoside reverse

transcriptase inhibitors

Adults and Children Estimated to be Adults and Children Estimated to be Living with HIV/AIDS, end of 2002Living with HIV/AIDS, end of 2002

Total: 42 million

Western Europe

570 000570 000North Africa & Middle East

550 000550 000Sub-Saharan

Africa

29.4 29.4 millionmillion

Eastern Europe & Central Asia

1.2 million1.2 million

South & South-East Asia

6 million6 million

Australia & New Zealand

15 00015 000

North America

980 000980 000Caribbean

440 000440 000

Latin America

1.5 1.5 millionmillion

East Asia & Pacific

1.2 million1.2 million

Regional HIV/AIDS Statistics and Features, Regional HIV/AIDS Statistics and Features, end of 2002end of 2002

Epidemic started

Sub-Saharan Africa

North Africa & Middle East

South and South-East Asia

East Asia & Pacific

Latin America

Caribbean

Eastern Europe & Central Asia

Western Europe

North America

Australia & New Zealand

late ’70searly ’80s

late ’80s

late ’80s

late ’80s

late ’70searly ’80slate ’70s

early ’80s

early ’90s

late ’70searly ’80slate ’70s

early ’80slate ’70s

early ’80s

29.4 million

550 000

6.0 million

1.2 million

1.5 million

440 000

1.2 million

570 000

980 000

15 000

8.8%

0.3%

0.6%

0.1%

0.6%

2.4%

0.6%

0.3%

0.6%

0.1%

58%

55%

36%

24%

30%

50%

27%

25%

20%

7%

Hetero

Hetero, IDU

Hetero, IDU

IDU, Hetero, MSM

MSM, IDU, Hetero

Hetero, MSM

IDU

MSM, IDU

MSM, IDU, Hetero

MSM

Adults & childrenliving with HIV/AIDS

Adult prevalence

rate *

% of HIV-positive

adults who are

women

Main mode(s) of transmission for those living with

HIV/AIDS **

Adults & children newly

infected with HIV

3.5 million

83 000

700 000

270 000

150 000

60 000

250 000

30 000

45 000

500

Epidemic started

Global Summary of the HIV/AIDS Epidemic, Global Summary of the HIV/AIDS Epidemic,

end of 2002end of 2002

Number of people living with HIV/AIDS Total 42 millionAdults 38.6 million Women 19.2 millionChildren under 15 years 3.2 million

People newly infected with HIV in 2002 Total 5 millionAdults 4.2 million Women 2 millionChildren under 15 years 800 000

AIDS deaths in 2002 Total 3.1 millionAdults 2.5 million Women 1.2 millionChildren under 15 years 610 000

Injection drug use32%

Heterosexualtransmission

66%

32%

Heterosexualtransmission

66%

Estimated* AIDS Incidence in Women and Adolescent Girls, by Exposure Category, Diagnosed in 2001,

United States

* Data adjusted for reporting delays and estimated proportional redistribution of cases initially reported without risk. Data reported through June 2002.

** Includes patients whose medical record review is pending; patients who died, were lost to follow-up, or declined interview; and patients with other or undetermined modes of exposure.

† Includes sex with a bisexual male, a person with hemophilia, a transfusion recipient with HIV infection, or an HIV-infected person with an unspecified risk

Other/not identified**3%

†

Sex with men ofother or

unspecified risk50%

Sex withinjection drug user

16%


• Areas of Discussion– trial design

• phase 2/3 run-in vs other designs• single trial vs 2 adequate and well controlled

trials

– control arms and criteria of a “win”• placebo and no-treatment controls

– trial duration• capture efficacy endpoints, assess durable

treatment effect and have long term safety experience

Clinical Trial Design Issues Clinical Trial Design Issues in the Development of Topical Microbicides in the Development of Topical Microbicides

for the Reduction of HIV Transmissionfor the Reduction of HIV Transmission

8:30 a.m. HIV and STIs in Women: Salim Karim, MBChB, Ph.D.

The Urgent Need for an Efficacious University of Natal

Microbicide Durban, South Africa

8:50 a.m. Lessons Learned from COL-1492, Lut Van Damme, M.D., MSc.

a Nonoxynol-9 Vaginal Gel Trial Contraceptive Research and

Development Program (CONRAD)

Arlington, VA

9:10 a.m. Considerations for Topical Teresa C. Wu, M.D., Ph.D.

Microbicide Phase 2 and 3 Trial Medical Officer

Designs, a Regulatory Perspective DAVDP, FDA

9:30 a.m. Considerations for Topical Andrew Nunn, M.D.

Microbicide Phase 2 and 3 Trial Medical Research Center

Designs, an Investigator’s London, UK

Perspective

10:25 a.m. Statistical Considerations for Thomas Fleming, Ph.D.

Topical Microbicide Phase 2 and Chair, Department of Biostatistics

3 Trial Designs, an Investigator’s University of Washington

Perspective Seattle, WA

10:50 a.m. Statistical Considerations for Rafia Bhore, Ph.D.

Topical Microbicide Phase 2 and Mathematical Statistician

3 Trial Designs, a Regulatory Division of Biometrics, FDA

Perspective

topical microbicides antiviral drugs advisory committee august 20, 2003

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