Merck to begin Phase 3 trials for investigational once monthly HIV prevention pill

“According to UNAIDS, 1.3 million people acquired HIV in 2023, highlighting the continued need for new PrEP options like our investigational once-monthly, oral PrEP candidate MK-8527, especially among women in sub-Saharan Africa and men who have sex with men, who experience disproportionately high rates of HIV,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Our collaboration with the Gates Foundation will help us explore the potential of MK-8527 to contribute to global efforts to reduce the number of HIV infections and help support opportunities to accelerate access around the world.”

The decision to initiate the Phase 3 clinical trial program was supported by the results of a double-blind, multicenter, Phase 2 trial (MK-8527-007, NCT 06045507) examining the safety and pharmacokinetics of MK-8527. The study enrolled 350 participants, 18–65 years of age, with low likelihood of HIV-1 exposure, who were randomized 2:2:2:1 to receive MK-8527 (3, 6, or 12 mg) or placebo once monthly for six months. In the trial, the rates of adverse events were similar among those in the MK-8527 arms and those in the placebo arm, and no clinically meaningful changes were seen in laboratory tests, including total lymphocyte and CD4 T-cell counts. The pharmacokinetics of MK-8527 and MK-8527-TP, the active form of MK-8527, support the continued development of MK-8527 as an oral, once-monthly option for PrEP. Results from the Phase 2 trial were highlighted in the opening press conference for IAS 2025, the 13th International AIDS Society Conference on HIV Science in Kigali, Rwanda, on Monday, July 14, at 15:30 – 16:30 CAT, titled “Breakthroughs Amid Crisis: The Future of HIV Innovation.” These research findings will be further detailed in a late-breaker oral session on Wednesday, July 16, at 12:15 – 13:15 CAT.

“Scientific advances against HIV have brought us further than ever imagined and are ushering in a new era in HIV prevention,” said Trevor Mundel, president of global health at the Gates Foundation. “With only 18% of global PrEP need currently met, there is a clear and urgent need for options like MK-8527 that may offer the ability to prevent infection. These Phase 3 trials are a key step toward translating progress into longer-acting options that could help turn the tide on HIV.”

In the EXPrESSIVE-10 trial, the International Clinical Research Center (ICRC) within the University of Washington Department of Global Health, in partnership with the University of Alabama at Birmingham, will receive grant funding from the Gates Foundation to support ICRC’s collaboration with 31 clinical research trial sites in Kenya, South Africa, and Uganda; sites will inform and engage communities and recruit, enroll, and follow women who participate in the EXPrESSIVE-10 trial.

Merck will be the trial sponsor, gaining regulatory and customs approvals, and providing operational expertise and resources for management of the trials. The Gates Foundation will also provide support for global community advisory groups, which will offer insight into community perspectives on a monthly PrEP pill, participant recruitment materials and strategies, and cultural considerations for these trials. Separately, the Gates Foundation will provide grant funding for EXPrESSIVE-11 to support the establishment of a community advisory group and the development of recruiting and retention materials only.