The non-profit International Partnership for Microbicides (IPM) has announced that it has voluntarily withdrawn its New Drug Application (NDA) for the dapivirine vaginal ring (DVR) for HIV prevention among cisgender women from the USA Food and Drug Administration (USFDA). This decision was made following feedback during the agency’s review that current data are unlikely to support USA approval at this time, given the current HIV epidemiology and the prevention landscape for women in the United States of America.
The DVR is a long-acting, women-controlled vaginal ring that slowly releases a antiretroviral (ARV) drug, dapivirine, locally in the vagina over one month. Two Phase III clinical trials – the Ring Study (IPM-027) and ASPIRE (MTN-020) – found that the DVR reduced women’s risk of HIV infection by about 30% with few adverse events and no safety concerns with long-term use (1,2). Two subsequent open-label extension (OLE) studies – DREAM and HOPE – showed increased ring use compared to the Phase III trials and suggested greater risk reduction by over 50% across both OLEs (3,4). Further exploratory analyses suggest even higher protection may be possible with consistent use of the ring (5), and the REACH study (MTN-034) found that high adherence can be achieved among adolescents and young women aged 16–21 (6).
In 2020, the dapivirine ring received a positive scientific opinion from the European Medicines Agency (EMA) under Article 58, or EU medicines for all (7), for its use among women at high risk for HIV who are unable to use daily oral PrEP (8). Under Article 58, the EMA can provide a scientific opinion on high priority human medicines that are intended for markets outside of the European Union (EU). This aims to facilitate access to essential medicines in low- and middle-income countries, including new or improved therapies for unmet medical needs, to prevent or treat diseases of major public health interest (9).
In January 2021, WHO made a conditional recommendation to offer the DVR as a safe and effective additional prevention choice for women at substantial risk of HIV infection as part of combination prevention approaches. As a result, WHO was able to include the DVR in the WHO list of prequalified medicines under the EMA Article 58 label using the alternative listing procedure.
The USFDA decision is not based on any new or additional data on efficacy or safety. WHO will continue to support countries as they consider whether to include the DVR as an additional prevention option for women. WHO recognizes that country decision making will vary based on their context and that women’s voices remain central to discussions about their prevention choices.
- Nel A, Bekker L-G, Bukusi E, et al. Safety, acceptability and adherence of dapivirine vaginal ring in a microbicide clinical trial conducted in multiple countries in sub-Saharan Africa. PLoS One. 2016;11:e0147743.
- Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. 2016;375:2121-32.
- Nel A, van Niekerk N, Van Baelen B, et al. Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study. Lancet HIV. 2021;8:e77–86.
- Baeten JM, Palanee-Phillips T, Mgodi NM, et al. Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study. Lancet HIV. 2021;8:e87–95.
- Brown ER, Hendrix CW, van der Straten A, T et al. Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV‐1 acquisition: a secondary analysis from a randomized, placebo‐controlled trial. J Int AIDS Soc. 2020;23:e25634.
- Nair G, Ngure K, Szydlo D, et al. Adherence to the dapivirine vaginal ring and oral PrEP among adolescent girls and young women in Africa: interim results from the REACH study. IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021. Abstract OALC01LB01.
- Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Text with EEA relevance). https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:32004R0726.
- EMA’s human medicines committee (CHMP) has adopted a positive opinion for Dapivirine Vaginal Ring (dapivirine) used to reduce the risk of infection with the human immunodeficiency virus type 1 (HIV-1), in combination with safer sex practices when oral pre-exposure prophylaxis (PrEP) is not used, cannot be used or is not available. https://www.ema.europa.eu/en/news/vaginal-ring-reduce-risk-hiv-infection-women-non-eu-countries-high-disease-burden.
- https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/public-guidance-parallel-application-eu-m4all-article-58-opinion-centralised-marketing-authorisation_en.pdf .