Jul22

FROM THE PIPELINE | Fast track to an MPT: Development of a dual-purpose pill containing oral PrEP and an oral contraceptive

Monday, 22 July 2019

Imagine if women could take one pill every day and be protected from unintended pregnancy AND HIV? 

And what if this pill was available within several years? 

We believe the fastest route to a contraceptive MPT is to combine two products that are ALREADY ON THE MARKET into a single pill.

A dual-purpose pill has the potential to play an important role in helping women protect themselves against both unintended pregnancy and HIV infection.

The Population Council is working with partners to fast-track development of dual- purpose pill

Young women worldwide are confronted with two significant health risks: unintended pregnancy and HIV infection. Over 215 million women worldwide – and 21% of women in sub-Saharan Africa – have an unmet need for contraception. Women in sub-Saharan Africa disproportionately shoulder the burden of the HIV epidemic, where nearly two thirds of new infections occur in young women. Although oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, uptake and adherence have been challenging in clinical trials and demonstration projects, especially in young women.

When asked, women tell us that they would be much more likely to use an HIV prevention product if it was also a contraceptive, i.e. a multipurpose prevention technology (MPT). The desire for an MPT aligns with higher rates of adherence seen in clinical trials of contraceptive products versus HIV prevention products. An MPT that prevents both HIV and unintended pregnancy would help overcome barriers to negotiating condom use and adherence issues related to stigma and gender dynamics seen in microbicide and PrEP trials. Several novel contraceptive MPTs are in development, yet it will be many years before one is available.

At the Population Council, with support from the Children’s Investment Fund Foundation (CIFF), we have been working to develop a single pill that delivers oral PrEP and a combined oral contraceptive (COC). Combining two approved products into a single dual-purpose pill is likely to be the fastest route to creating a female-initiated MPT, with the potential to enhance uptake of PrEP, especially among current oral contraceptive users. Our goal is to develop a 28-day dual-purpose pill for women at risk of both unintended pregnancy and HIV.

To accelerate the development of the dual-purpose pill, we have taken a two-pronged approach: 1) over-encapsulating PrEP and a COC in a single pill for acceptability testing; and 2) co-formulating a single tablet containing the same four active pharmaceutical ingredients (APIs) that are in PrEP and a COC. The Population Council is also evaluating a co-formulation of a COC with both Truvada®, currently approved for PrEP, and Descovy®, in the event Descovy is approved for PrEP in women. If approved, Descovy would be the preferred HIV prevention component since the pill is smaller. Women would receive a blister pack containing 21 co-formulated dual-purpose pills (Truvada or Descovy plus COC) and 7 tablets of Truvada or Descovy (no COC), which corresponds to a 28-day contraceptive regimen.

Over-encapsulation: A six-month crossover acceptability study is a strategy to jump start the product introduction process. We are planning a crossover study among 30 adolescent girls and young women (AGYW) in Zimbabwe, where COCs are used by nearly 50% of women using modern contraceptives. All 30 women will be enrolled for six months and will use the over-encapsulated PrEP plus COC for 3 menstrual cycles. For the other three menstrual cycles, women will take two separate pills. Women will be randomized to the SEQUENCE (single capsule versus two separate pills). At the end of the study, we will determine women’s preferred regimen and will evaluate whether adherence is better with the single capsule versus the two separate pills. The study will also include in-depth interviews with health care providers and key opinion leaders about introducing a dual-purpose pill in Zimbabwe.

Co-formulation: With funding from CIFF, we have started working on co-formulating a stable dual-purpose pill with the Truvada APIs (tenofovir disoproxil fumarate and emtricitabine) and the COC APIs (levonorgestrel and ethinyl estradiol). This effort is likely to take 12-18 months. Once a stable tablet seems likely, the path to regulatory approval will be negotiated with the FDA. One proposal for discussion with the FDA is to file the 28-day dual-purpose pill regimen as a 505(b)(2) supported by a single bioequivalence-type study. The absence of a cure for HIV makes prevention of HIV very important to public health and this fact provides the optimism for the 505(b)(2) approach.

By our conservative estimates, over 1 million women a year would benefit from this dual- purpose pill representing less than 2% of women currently using COCs in high HIV prevalence countries (Population Council, unpublished market research data). This dual-purpose pill would be the first pharmaceutical MPT in women’s hands for prevention of both unintended pregnancy and HIV prevention.


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About the Population Council
The Population Council’s mission is to improve the sexual and reproductive health and well-being of current and future generations and to help achieve a humane, equitable, and sustainable balance between people and resources. Through biomedical, social science, and public health research in over 50 countries, we work with our partners to deliver solutions that lead to more effective technologies, programs, and policies that improve lives worldwide.

About the Author

Barbara Friedland

Barbara Friedland is an associate in the Population Council’s HIV and AIDS program. Friedland has been involved in both clinical and behavioral research, primarily focused on HIV prevention. She has also coordinated several international clinical trials of the Council’s first candidate microbicide, Carraguard®, and is currently managing the first in-human study of the Council’s ARV-based microbicide, PC-1005 (MIV-150 and zinc acetate in a carrageenan gel).

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