Topical Microbicides

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Topical Microbicides

• Antiviral Drugs Advisory Committee
• August 20, 2003

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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

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Topical Microbicides

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

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Topical Microbicides

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

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Adults and Children Estimated to be Living with
HIV/AIDS, end of 2002
Eastern Europe Central Asia 1.2 million
Western Europe 570 000
North America 980 000
East Asia Pacific 1.2 million
North Africa Middle East 550 000
South South-East Asia 6 million
Caribbean 440 000
Sub-Saharan Africa 29.4 million
Latin America 1.5 million
Australia New Zealand 15 000
Total 42 million
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Regional HIV/AIDS Statistics and Features, end
of 2002
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
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
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
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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
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Heterosexual
transmission
66
Injection drug use
32
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
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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

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Clinical Trial Design Issues in the Development
of Topical Microbicides for the Reduction of HIV
Transmission

• 830 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
• 850 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
• 910 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
• 930 a.m. Considerations for Topical
  Andrew Nunn, M.D.
• Microbicide Phase 2 and 3 Trial
  Medical Research Center
• Designs, an Investigators
  London, UK
• Perspective