Rectal Microbicide Development
FDA Antiviral Advisory Committee
20 August, 2003
Ian McGowan M.D., Ph.D.
Center for HIV & Digestive Diseases at
David Geffen School of Medicine,
• Why develop rectal microbicides?
• What are the challenges in rectal
• What is the current status of rectal
Why Develop Rectal Microbicides?
• Anal intercourse (AI) is the primary risk factor for
HIV transmission among MSM.
• The prevalence of AI among the heterosexual
population is underappreciated and represents a
significant risk for HIV transmission.
• Much AI is unprotected.
• The rectal mucosa is highly vulnerable to HIV
• Based on the N-9 experience, vaginal products
may not be suitable for rectal administration.
Prevalence of Anal Receptive Sex
Population N Prevalence of Reference
MSM in 4295 48 – 54% Koblin et al. 2003
High risk 1268 32% Gross M et al.
College 210 20% Civic D 2000
Californian 3545 6-8% Erickson PI et al.
What are the Challenges in Rectal
• Creating awareness that rectal microbicide
development is needed
• Development strategy not defined
– Vaginal products
– Rectal products
– Combination Rectal & vaginal products
• Safety evaluation of candidate rectal
microbicides not established
Vaginal Microbicide Pipeline
Design of rectal studies
Phase1 needed to support
rectal studies a vaginal
Are Conventional Safety Studies
Sufficient for Rectal Microbicides?
What is the Current Status of
Rectal Microbicide Development?
• N-9 has been shown to be unsafe as a
• Carraguard™ did not induce epithelial
• No Phase 1 microbicide studies are
• There is an urgent need to develop rectal
microbicides for the MSM population
• Anal intercourse is an underappreciated risk
factor for HIV transmission in heterosexuals
• Vaginal microbicides need to be evaluated in the
rectal compartment prior to NDA approval.
• Rectal microbicides require an appropriate
preclinical and clinical development track