1. Rectal Gels for PrEP Are They an Option?
Ian McGowan MD DPhil FRCP University of Pittsburgh, PA, USA 24th July, Paris, France

2. Overview What are rectal microbicides? Are they needed?
Where is the science?
What are the obstacles to the development of a safe and effective rectal microbicide?
Scientific
Regulatory
Programmatic
Rectal Gels for PrEP: are they an option?

3. What Are Rectal Microbicides?
Topical products that are designed to prevent, or significantly reduce, the acquisition of sexually transmitted diseases including HIV infection
Gels, enemas, or inserts
Daily administration or event driven use
Antiretroviral or non-antiretroviral

4. Rectal Microbicide Formulations

5. Are They Needed? People like choices e.g. contraception
Topical products are behaviorally congruent
Ideal approach for event driven use
No PrEP agent / formulation has a perfect TPP
But
Oral PrEP is licensed, safe, highly effective, and increasingly available
Dual compartment protection may require systemic administration of PrEP agents
Public health and research resources are limited

6. Where is the Science?
Good non-clinical animal model data to support the safety and effectiveness of topical PrEP agents including candidate rectal microbicides
Multiple products have advanced through Phase 1 evaluation generating supportive safety, acceptability, and PK/PD data
A tenofovir gel has been evaluated in a Phase 2 international multicenter study (MTN-017)
As of yet no Phase 2B/3 effectiveness studies

7. Would This Approach Work?
“HIV” (99mTc-SC) in Ejaculate
“Microbicide”(111In-DTPA)
CHARM-02 Study (Hiruy H et al. AIDS Res Hum Retroviruses 2015)

8. CHARM-01 Explant Data
McGowan I et al. PLoS ONE 2015

9. What are the obstacles to the development of a safe and effective rectal microbicide?

10. Scientific
Gels and inserts may not provide the comprehensive mucosal coverage needed to prevent HIV infection
Topical products may not provide mucosal and systemic protection
Men and women are at risk of HIV infection associated with condomless anal sex
Topical products are unlikely to provide dual compartment protection unless used in both compartments

11. What the Consumers Want

12. What They Get

13. Regulatory
With the increasing availability of oral PrEP the feasibility of conducting classical placebo controlled Phase 3 effectiveness studies has ended
The alternative design strategies are likely to require very large/expensive trial designs
Non-Inferiority (NI) studies
But HPTN-083 is a Phase 2B/3 NI Study (N=4,500) evaluating LA cabotegravir
In the absence of novel design strategies, demonstration of rectal microbicide efficacy may not be possible
WEWS02: How to Assess the Efficacy of New Strategies for the Prevention of HIV-infection?

14. Programatic Oral PrEP increasingly available
2nd generation oral PrEP FTC/TAF Study being funded by Gilead Sciences (the DISCOVER Study)
Antiretroviral intravaginal ring (dapivirine) positioned for regulatory review and potential licensure
LA PrEP (cabotegravir) in Phase 2B/3 development.
Data anticipated Q4 2021
What else do we need?

15. Dr. Carl Dieffenbach, February 2017

16. Rectal Gels for PrEP: are they an option?
Another option
Rectal Gels for PrEP: are they an option?