# Presentation: 216408

## Topical Microbicides

**Antiviral Drugs Advisory Committee**
**August 20, 2003**

## Topical Microbicides

**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 

**Ideal Characteristics**
**Non-irritating **
**Discreet **
**Odorless**
**Tasteless**
**Colorless**
**Stable in most environments**
**Affordable**
**Safe and Effective**

## Topical Microbicides 

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

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

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

**Total: 42 million**** **

**Western Europe**
**570 000**

**North Africa**
**    ****& Middle East**
**550 000**

**Sub-Saharan Africa**
**29.4 million**

**Eastern Europe ****& Central Asia**
**1.2 million**

**South **
**& South-East Asia**
**6 million**

**Australia **
**& New Zealand**
**15 000**

**North America**
**980 000**

**Caribbean**
**440 000**

**Latin America**
**1.5 million**

**East Asia & Pacific**
**1.2 million**

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

- 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 ’70s**
**early ’80s**
**late ’80s**
**late ’80s**
**late ’80s**
**late ’70s**
**early ’80s**
**late ’70s**
**early ’80s**
**early ’90s**
**late ’70s**
**early ’80s**
**late ’70s**
**early ’80s**
**late ’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**

**3.5  million**
**83 000**
**700 000**
**270 000**
**150 000**
**60 000**
** **
**250 000**
**30 000**
**45 000**
**500**

##  Global Summary of the HIV/AIDS Epidemic, end of 2002

**Number of people living with HIV/AIDS ****	****Total****	****42 million****	****Adults****	****38.6 million****	****   *****Women******	******19.2 million*****	****Children under 15 years****	****3.2 million **
**People newly infected with HIV in 2002  ****	****Total****	****5 million****	****Adults****	****4.2 million****	****   *****Women******	******2 million*****	****Children under 15 years****	****800 000**
**AIDS deaths in 2002 ****	****Total****	****3.1 million****	****Adults****	****2.5 million****	****   *****Women******	******1.2 million*****	****Children under 15 years****	****610 000**

## Injection drug use

- 32%

- Heterosexual

- transmission

- 66%

**32%**

- * 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

## Topical Microbicides

**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 in the Development of Topical Microbicides for 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