Rectal Microbicides Ian McGowan MD PhD FRCP
Magee Womens Research Institute University of Pittsburgh, USA
Overview What is a rectal microbicide? Who might use a rectal microbicide? How are we developing rectal microbicides? What studies are being conducted? When will we have a rectal microbicide to use?
What is a Rectal Microbicide?
Microbicides are products that can be applied to the vaginal or rectal mucosa with the intent of preventing or significantly reducing the risk of acquiring STIs including HIV
Microbicides are products that can be applied to the vaginal or rectal mucosa with the intent of preventing or significantly reducing the risk of acquiring STIs including HIV
A Bit About the Rectum
How Might a Rectal Microbicide Work?
McGowan I, Biologicals, 2006
What Would a Rectal Microbicide Look Like?
Who Might Use a Rectal Microbicide?
MSM
Women
Developed World
Percentage (%)
50 40 30 20 10 0
Seattle
Developing World
St. Louis New Orleans
How Do We Develop Microbicides?
The Good Old Days
Stages of Drug Development Phase 1 Small safety studies. Two week exposure with 2040 participants
Phase 2 Expanded safety. Three to six month study with 100 – 200 participants
Phase 2B/3 Efficacy study: One to two year study with 1,000 – 5,000 participants
Licensure
Phase 1 Design 2% N-9
7-14 day interval
7-14 day interval
(N=15)
N=60
1% Tenofovir
Baseline Evaluation
Single dose
7 day daily doses
(N=15)
HEC (N=15)
Screening
No Treatment (N=15)
Endoscopy Safety/behavioral assessment
Where Would We Conduct Phase 2/3 Studies? Phase 2 studies RAI sexually active men and women Higher risk populations
Phase 2B studies 3% seroincidence MSM populations North America Latin America (Peru, Brazil) Asia Pacific (Thailand) Africa (South Africa)
Drug Development is Expensive! $150M
$100M
$1M Phase 1
Phase 2
Phase 2B/3
Most Candidates Are Never Licensed
YEARS
15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0
POST-MARKETING SURVEILLANCE
MARKET LAUNCH
PHASES IV
1 DEVELOPMENT
2 2- 5 5 - 10 10 - 20
BASIC RESEARCH
10,000 - 100,000
CLINICAL TEST (HUMANS)
III II I
PRECLINICAL (ANIMALS) SYNTHESIS, EXAMINATION & SCREENING
QUANTITY OF SUBSTANCES Source: Based on PhRMA analysis, updated for data per Tufts Center for the Study of Drug Development (CSDD) database.
What Studies Are Being Conducted?
Rectal Specific Products CHARM Program Combination HIV Antiretroviral Rectal Microbicide Program DAIDS IPCP Program Tenofovir, UC781, tenofovir + UC781 Consortium University of Pittsburgh UCLA Johns Hopkins CONRAD PI: Ian McGowan MD PhD
Microbicide Safety and Acceptability in Young Men Stage 1A
Stage 1B
Stage 2
Screening
3 month Acceptability & Adherence study with placebo gel
Phase 1 VivaGel rectal safety study
120 MSM
42 MSM
RAI in last 3 months
80% adherence in Stage 1B
240 MSM Consensual RAI in last month URAI in last year
STI negative
McGowan & Carballo-Dieguez 2009
When Will We Have a Rectal Microbicide?
Prescription or Over-the-Counter?
Rectal Microbicide Timeline* 2010 2011 2012 2013 2014 2015 2016 2017 2018 Phase 1 Phase 2 Phase 2B
Review Available Vaginal microbicides
*An approximation based on 1% tenofovir
Bargello Museum, Florence, Italy