Merck to initiate Phase 3 trials for once-monthly HIV prevention pill

Merck (MRK) announced the initiation of the EXPrESSIVE Phase 3 clinical trials, evaluating the safety and efficacy of MK-8527, an investigational once-monthly, oral nucleoside reverse transcriptase translocation inhibitor for HIV pre-exposure prophylaxis. The EXPrESSIVE-11 trial will evaluate the safety and efficacy of MK-8527 among people with greater likelihood of HIV-1 exposure in 16 countries and will begin enrolling in August 2025. In collaboration with the Gates Foundation, the EXPrESSIVE-10 trial will evaluate the safety and efficacy of MK-8527 in women and adolescent girls in sub-Saharan Africa and will begin enrolling in the next few months. The decision to initiate the Phase 3 clinical trial program was supported by the results of a double-blind, multicenter, Phase 2 trial 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 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.