Biopharmaceutical company Merck & Co, Inc (NYSE: MRK), known as MSD outside the US and Canada, announced on Monday that it will initiate Phase 3 clinical trials for MK-8527, an investigational once-monthly oral HIV pre-exposure prophylaxis (PrEP) therapy.

The EXPrESSIVE-11 trial will begin enrolling in August 2025 across 16 countries, while the EXPrESSIVE-10 trial, focused on women and adolescent girls in sub-Saharan Africa, will begin enrolment in the coming months.

Both trials will evaluate the safety and efficacy of MK-8527 compared to daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), the current standard for PrEP. EXPrESSIVE-11 will enrol 4,390 participants, while EXPrESSIVE-10 will enrol 4,580 women aged 16–30 in Kenya, South Africa, and Uganda. Merck will sponsor the trials, with grant and advisory support from the Bill & Melinda Gates Foundation.

The decision to advance MK-8527 was based on data from a Phase 2 trial demonstrating strong safety and pharmacokinetics, with no significant adverse effects and robust systemic exposure. MK-8527 is a nucleoside reverse transcriptase translocation inhibitor (NRTTI), acting through multiple mechanisms including delayed chain termination.

Merck's HIV pipeline includes treatment and prevention options targeting the global burden of HIV, with MK-8527 positioned as a long-acting alternative to daily oral PrEP regimens. Full Phase 2 data were highlighted during the opening session of IAS 2025 in Kigali, Rwanda.