Gastrointestinal Complications of HIV Infection The Past_ the

					Rectal Microbicide Development

FDA Antiviral Advisory Committee
          th
      20 August, 2003

       Ian McGowan M.D., Ph.D.
  Center for HIV & Digestive Diseases at
    David Geffen School of Medicine,
                  UCLA
            Three Questions
• Why develop rectal microbicides?

• What are the challenges in rectal
  microbicide development?

• What is the current status of rectal
  microbicide development?
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
  infection.
• 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
                          AI
MSM in        4295     48 – 54%      Koblin et al. 2003
EXPLORE
study
High risk     1268       32%         Gross M et al.
women                                2000

College       210        20%         Civic D 2000
students

Californian   3545       6-8%        Erickson PI et al.
residents                            1995
What are the Challenges in Rectal
  Microbicide Development?
• 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
          Screening for
            Phase1
          rectal studies


                              Are Phase1
            Design of        rectal studies
             Phase1        needed to support
          rectal studies       a vaginal
                           microbicide NDA?
Are Conventional Safety Studies
Sufficient for Rectal Microbicides?

                                 CCR5
                               Expression
  What is the Current Status of
Rectal Microbicide Development?
• N-9 has been shown to be unsafe as a
  rectal microbicide
• Carraguard™ did not induce epithelial
  damage
• No Phase 1 microbicide studies are
  currently planned
                 Summary
• 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

				
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posted:7/14/2013
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