Part 1. What are MPTs & why do we need them?

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1 Faculty Disclosures Multipurpose Prevention Technologies (MPTs): The Intersection of Contraceptives, HIV & STDs Dr. Young Holt has no disclosures Bethany Young Holt, PhD MPH CAMI/Public Health Institute 21 May 2014 Women s Health Update 2014 Berkeley, CA Session Overview Part 1. What are MPTs and why do we need them? Part 2. Global need and regional priorities for MPTs. Part 3. The status of MPTs in development. Part 4. Innovative partnerships advancing the MPT field. Part 1. What are MPTs & why do we need them? Multipurpose Prevention Technologies Prevent a combination of unintended pregnancy, STIs, HIV/AIDS Should be safe & easily available Are designed with key input from women for their specific needs & preferences 1

2 Global Need Each year 1.7 million people die from AIDS and 2.5 million become infected. 1 million people contract a sexually transmitted infection every day. 222 million women have an unmet need for modern contraception. Each day, close to 800 women in developing countries die from complications related to pregnancy and childbirth. Case Study #1: Kajiata In the United States Age 33, married Lives in region with high rates of HIV and HSV-1 Already has 6 children Currently gets the Depo injection Husband spends a significant amount of time out of the village and she accepts he is Every 60 unfaithful seconds a young woman is Husband infected will with not HIV. wear a condom Nearly half of all pregnancies among American women are unintended. STIs are the most commonly reported communicable diseases in the US. There are18.9 million new cases of STIs each year in the US. CA Teen Birth Rates by Chlamydia Rates Consequences of STIs Source: Ctr for Research on Adolescent Health and Development STIs enhance the biological risk for HIV infection and transmission and can impact how the disease progresses. Long-term health consequences of STIs include: Cervical cancer Pelvic inflammatory disease Infertility Tubal or ectopic pregnancy Infants born to infected mothers can suffer from perinatal or congenital infections 2

3 Case Study #2: Angie Age 19 Lives in region of the US with high incidence of chlamydia Currently using long acting reversible contraception No longer in a committed relationship 1 million people Doesn t contract always a sexually use a transmitted infection condomeveryday. Part 2. Global need, regional priorities Complex Factors = Many Possibilities Why Develop a Target Product Profile (TPP) for MPTs? Conditions Pregnancy, HSV, HPV, HIV, BV, Chlamydia, Gonorrhea, Syphilis, Candida, Trich Product Types Vaginal film, Vaginal tablet, Oral tablet, Vaginal ring, Non-IVR device, Vaginal gel, Injectable, Implantable MPT Product Possibilities Delivery Methods Topical daily, Topical pericoital, Systemic sustained, Topical sustained, Oral daily, Oral pericoital Actions HC, Non-HC, Barrier, Pro-biotic, Antimicrobial, Antifungal, Antiviral Image source: Example of an MPT TPP Product Specificity Indications: HIV + Unintended Pregnancy API: Hormone(s) Small Molecule ARV Dosage Forms: IVR LA Injectable On-Demand Label Attributes Indications Target Populations Target Efficacy Presentation Dimensions, appearance, etc. Stability, storage, shelf life Preclinical Safety/Pharmacology Clinical Safety/Pharmacology PK/PD Contraindications/Acceptable AE Profile Other market relevant attributes Cost, etc. MPT Product Specific TPP: IVR Example Clinical Safety No vaginal epithelial damage; ; no systemic toxicity; no meaningful effects on the FGT microbiome, transcriptome, or proteome; no significant induction of inflammatory response markers; no unacceptable effects on daily life style or schedule; no social harm effects/aes Necessary Studies, Trials, Data Appropriate Phase 1 thru Phase 3 clinical trials with appropriate pharmacovigilance studies post approval. Annotations The minimally acceptable general safety yprofile should be equivalent to current comparable products (e.g. Nuvaring, or other HC contraceptive based products and currently available ARV treatment products). 3

4 How Are Regional MPT Priorities Defined? Assessment of available regional surveillance data Unintended pregnancy HIV Other STIs Solicit input from regional experts Development of Target Product Profiles (TPPs) As a health care provider Q1. Which of the following is your highest priority for MPT development: a) HIV b) Family Planning c) STIs (non- HIV) Provider Answers to Question #1: Which of the following is your highest priority for MPT development? African providers ranked unintended pregnancy + HIV as highest (65.7%) US providers ranked unintended pregnancy + other STIs as highest (66.3%) Africa US As a health care provider Q2. Other than HIV, preventing which of the following STIs is your highest priority? a) Herpes simplex d) Gonorrhea HSV e) Chlamydia b) Papilloma Virus f) Syphilis HPV g) Trichomonas c) Bacterial Vaginosis BV Source: USAID Provider Answers to Question #2: Other than HIV, preventing which of the following STIs is your highest priority? African providers ranked HPV as highest (75.1%) US providers also ranked HPV as highest (68.1%) Africa US As a health care provider Q3. Which dosage form for a combination product would be most accepted and used by your clients? a) Topical, right d) Sustained Release before sex Device b) Topical, once/day e) Injectable/Implant c) Oral pill f) Implant Source: USAID 4

5 Provider Answers to Question #3: Which dosage form for a combination product would be most accepted and used by your clients? African providers ranked injection and sustained release device slightly higher than others (22.2% and 19.7%, resp.) US providers ranked oral dosage highest (46.2%) Africa US Varying regional MPT priorities MPT Stakeholders Washington, DC Nov, 2011 n= ~120 32% 11% 57% Family Planning Experts Dakar, Senegal Dec, % n= ~300 25% 66% 25 % US Reproductive Health Care Providers Sept, 2011 n= ~600 17% 40% 43% Source: USAID Potential Challenges for Research and Development Preclinical: What nonclinical studies are needed? Manufacturing: additional manufacturing steps required Use of new polymers Qualify and obtain high quality supplies Regulatory: Combination and multiple indication products with a delivery device. Bridging versus bioequivalence Clinical: Prevention of pregnancy and HIV/STI infection are very different clinical trials Social and Behavior: Is coupling contraception with anti-hiv/sti a slam dunk Demand creation Adolescence use Access Delivery channels (last mile!) Policies and practices of the procuring entity Part 3. What s the status of MPT development? MPTs: Historical Precedents Currently Available MPTs H2O + flouride The pill + iron Grains + folic acid Male Condom Female Condom ADVANTAGES: Available now DISADVANTAGE: Use rates are low, difficult to negotiate 5

6 Priorities for 1 st Generation MPTs On-Demand Products On-Demand Sustained Release Long-acting Injectable Tenofovir Gel (CONRAD) Electrospun Nanofibers Used around time of intercourse For women who have intermittent sex or want more direct control over their protection User-initiated, does not require daily action Should increase adherence and effectiveness Co-administration of products targeting separate indications Equal duration of effectiveness for the co-administered products 1 st proof-of-concept vaginal microbicide Coitally-dependent Confirmation trial underway for 2014 Novel formulation of active drugs in thin film-type configuration Combination via film layering Vaginally administered w/o applicator On-Demand (pericoital) Products Sponsor Product Target Status CONRAD 1% TFV Gel HIV/HSV Proof of concept CAPRISA 004 PATH SILCS HIV, HSV, Phase 1 TFV 1% Diaphragm + TFV Contraceptive gel Prototype: +/- HC gel contraceptive TFV 1% gel Anderson IPCP Film + mab HSV, HIV Planned Phase 1 Yazo Biotechnologies SAMMA gel Contraceptive, HSV, HIV, HPV, Chlamydia, N. gonorrhea Prototype CAPRISA 004: Impact of tenofovir gel on HSV-2 incidence Tenofovir gel n = 202 * Placebo gel n = 224 * # HSV-2 infections Women-years of follow up HSV-2 incidence per 100 wy (95% CI) 9.9 (6.6, 14.2) * Note: Excludes equivocal HSV-2 results at study exit IRR = 0.49 (CI: 0.30, 0.78); P = (15.3, 26.1) 51% protection against HSV-2 by tenofovir gel (CI: 22%-70%) Abdool Karim Q, et al. AIDS Abstract TUSS0502. Sustained Release Devices: Combination Intravaginal Rings 60-day Dapivirine + LNG (IPM) DPV + LNG Early development underway, clinical studies 2015? Pregnancy, HIV Nuvaring Type MPT Technology Novel polymer/co-extrusion IVR Multiple API delivery Established scale-up manufacturing system IVR Based MPTs Contraception & HIV Sponsor CONRAD IPM Population Council Biorings Albert Einstein College Auritec Merck Auritec CONRAD IVR PU segmented. LNG/TFV. Silicon. LNG/Dapivirine Polymer? Carrageenan, Zn Acetate, MIV-150, LNG. Targeting HPV+HSV+HIV. Prototype. Hydrophilic polymeric hydrogel; Ferrous Gluconate Acrobic Acid - Polyamino-Polycarboxlic Polycarboxlic acid -Boc-Lysinated Betulonic Acid or TFV PU segmented. LNG/TDF POD. HC+ARV. EVA HC (tbd), Vivicviroc, MK2048 POD. HC+Acyclovir. Targeting HSV> Prototype Acyclovir alone; Phase 1 completed PU LNG/TFV. Targeting HSV+HIV, phase 1 planned 6

7 MPT Long Acting Injectables 2 or more drugs administered to the subject simultaneously Depo Provera Long-acting Injectable ARVs Rilpivirine S/GSK 744 Cyclofem + Other HC and non-hc MPTs in the Pipeline Small Organic Molecules Broad Spectrum Natural Products Proteins/Peptides Non-Hormonal Contraceptives Single & Multipurpose Vaccines Today: Single purpose vaccines (HPV & HBV) 20 years: Multivalent vaccines (HSV, HIV, Gonorrhea, Chlamydia, Trichomonas, other STIs) Contraceptive vaccines are not likely To learn more For additional details on the individual products in this presentation: MPT Product Development & Regulatory Issues Live webinar featuring Dr. Joseph Romano 101 (NWJ Group/CAMI) & Dr. Jim Turpin (NIAID) Available at Searchable Online MPT database Searchable Online MPT database 7

8 Part 4. Innovative partnerships advancing the MPT field MPT Products/Field are Complex Product Stakeholders R & D Groups Funders Advocates Industry End Users Providers MPT Development Commercialization Acceptability Delivery Product Complexity Indications Drugs Dosage Forms Use Regimen Access Procurement Rationale for Funding Coordination IMPT Collaboration Structure R&D Total $$: ~$250M Clinical Testing Product Intro Total $$: ~$75M Product Intro 1 $ % success rate $ % success rate $ Ongoing Total time: ~15 years Time: ~7 years Source: USAID What you can do Learn more about MPTs visit: MPT g 8

9 Acknowledgements Anke Hemmerling (UCSF/CAMI) Laura Vyda (SparkAction/CAMI) Joseph Romano (RWJ Group/CAMI) Kathryn Stewart (CAMI) Laura Dellplain (CAMI) Questions? Funders: BMGF Mary Wolhford Foundation USAID Thank you! Support for this project is made possible by the generous support of the American people through the United States Agency for International Development (USAID) under the terms of the HealthTech Cooperative Agreement #AID-OAA-A , managed by PATH. The contents are the responsibility of CAMI/PHI and its partners and do not necessarily reflect the views of USAID or the US Government. 9