The Present and Future of Microbicides Jim Pickett

The Present and Future of Microbicides Jim Pickett, AFC/IRMA Los Angeles Biomedical Forum May 31, 2013

Our time together… • Microbicides – What are they? – Vaginal microbicide research – Rectal microbicide research • IRMA – Who is she? – Rectal microbicide advocacy

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Microbicides 4

What is a microbicide? • A product applied topically in the vagina or the rectum that can offer protection against HIV and, ideally, other STI pathogens • Ideally would have a contraceptive version, and another to allow for pregnancy – ARV/non-ARV (MPTs) • Formulated as a gel/lubricant, film, or vaginal ring • A rectal microbicide might be delivered via gel/lubricant, douche/enema, or … Microbicides are still in development they are not available yet!

How a microbicide works Mc. Gowan I, Biologicals, 2006 Slide courtesy Dr. Ian Mc. Gowan

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Vaginal microbicide research CAPRISA 004 9

South Africa 2 sites in Kwa. Zulu-Natal The trial achieved a Phase IIB - 889 HIV- women, 18 – 40 80% + compliance = 54% efficacy Enrolled May 2007 – Jan. 2009 Vaginally formulated tenofovir gel Results July 20, 2010 – AIDS 2010 95% retention rate

Vaginal microbicide research • CAPRISA 004 – HUZZAH! – CAPRISA 008 • Implementation study underway • Effectiveness/sustainability in rural and urban clinics • HIV-negative CAPRISA 004 participants 11

Vaginal microbicide research • VOICE • Phase 2 B, randomized, double-blind, placebo-controlled, 5 -arm trial • 5029 women in trial – Uganda, South Africa and Zimbabwe • Studied daily use of following : – Vaginal tenofovir 1% gel – Oral tenofovir – Oral Truvada • Results announced March 2013 CROI 12

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The Big 3 – Effectiveness Trials • Phase III trial of tenofovir gel • BAT 24 dosing – hope to confirm CAPRISA 004 • 2600 women, age 18 -30, SA 10 sites • Oct 2011 ~ mid 2014 Monthly vaginal ring with Dapivirine – 2 IPM trials 023/The Ring ASPIRE/MTN 027, P Study III • Phase III • 1650 women • South Africa, Rwanda • Apr 2012 ~ mid • Phase III • 3500 women • Malawi, SA, Uganda, Zambia, Zimbabwe • July 2012 ~ end 2014 Slide courtesy AVAC

Anal intercourse is a human behavior.

An act of unprotected anal intercourse is 10 to 20 times more likely to result in HIV transmission than an act of unprotected vaginal intercourse.

Rectal microbicide research • RMP 01 – UC-781 • 36 men/women U. S. • MTN 006 – tenofovir • 18 m/w U. S. • MTN 007 – modified tenofovir • 65 m/w U. S. • Project Gel, CHARM SOON MTN 017 • 186 Peru, RSA, Thailand, U. S. , PR (gay, MSM, TG women) 18

NICHD R 01: Ian Mc. Gowan & Alex Carballo-Dieguez

RM Safety, Acceptability /Young Men Stage 1 A Stage 1 B Screening 3 month Acceptability & Adherence study with placebo gel 240 MSM Consensual RAI in last month URAI in last year Stage 2 120 MSM Phase 1 Tenofovir rectal safety study RAI in last 3 months 24 MSM STI negative R 01 HD 059533 Slide courtesy Dr. Ian Mc. Gowan

CHARM Program • Combination HIV Antiretroviral Rectal Microbicide Program • Development of rectal specific ARV microbicides • Humanized mouse model • Phase 1 studies – Tenofovir – Maraviroc – Tenofovir & Maraviroc Slide courtesy Dr. Ian Mc. Gowan, pic from the IRMA collection

CHARM 01 • Phase 1 rectal safety study • Tenofovir 1% gel – Original formulation (3, 111) – Reduced glycerin formulation (846) – Rectal specific formulation (479) • Endpoints – Safety, – Acceptability, – PK/PD • N = 18 • Sites – Pittsburgh – UCLA • Q 1 2013 Slide courtesy Dr. Ian Mc. Gowan

CHARM 02 • Phase 1 rectal safety study • Safety in the presence or absence of simulated coitus • Endpoints – Safety – PK – Product distribution • N=9 • Sites – Johns Hopkins • Q 1 2013 Slide courtesy Dr. Ian Mc. Gowan

CHARM 03 • Phase 1 rectal safety study • Maraviroc • CCR 5 antagonist (Selzentry®) • Study products – Maraviroc 0. 1% – Maraviroc 1. 0 % – Maraviroc + tenofovir • Endpoints – Safety, – Acceptability, – PK/PD • N = 24 • Sites – Pittsburgh – UCLA – Johns Hopkins • Q 1 2014 Slide courtesy Dr. Ian Mc. Gowan

MTN-017 – Any day now… 8 weeks Gel Daily 8 weeks Gel With Sex 8 weeks Oral Truvada Gel With Sex Gel Daily Real-time PK monitoring Slide courtesy Dr. Ian Mc. Gowan

) l e g e h t ( To enjoy ed e n u o y t s r fi to use it 26

Who is IRMA? 27

IRMA, b. 2005 4 people, 4 agencies, 2 countries 28

1200+ advocates, scientists, funders, policymakers from 6 continents AIDS Foundation of Chicago is the IRMA secretariat 29

Mission: support development of safe, effective, acceptable, and accessible rectal microbicides for all that need them AIDS Foundation of Chicago is the IRMA secretariat 30

Highly active moderated listserv Focused projects in Africa, S. America Materials and Presentations Website Blog, Facebook, Twitter, You. Tube Global teleconferences 31

Highly active moderated listserv You haven’t lived if you’re not on the IRMA list. Linda-Gail Bekker, Desmond Tutu HIV Foundation 32

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irma-rectalmicrobicides. blogspot. com 35

You. Tube tinyurl. com/Rectal. Rev. English tinyurl. com/Rectal. Rev. Spanish tinyurl. com/Rectal. Rev. Thai 36

rectalmicrobicides. org 37

Monograph being published by RAND – coming to you soon electronically, and featuring a forward by Archbishop Desmond Tutu. Visit www. mappingpathways. blogspot. com

Thanks to our supporters • AIDS Foundation of Chicago • amf. AR – The Foundation for AIDS Research • Broadway CARES /Equity Fights AIDS • Elton John AIDS Foundation • New Venture Fund • NIH Office of AIDS Research • AVAC • MAC AIDS Foundation • Microbicide Trials Network • Population Council • Individuals - like my partner 39

Thank you xxoo Don’t be a stranger jpickett@aidschicago. org 40

Questions/comments? 41