Key takeaways
- Merck has launched the Phase III EXPrESSIVE program to evaluate MK-8527, a once-monthly oral PrEP candidate, in populations at high risk for HIV, including women and adolescent girls in sub-Saharan Africa.
- Both EXPrESSIVE-10 and -11 are large, randomized, active-controlled trials comparing MK-8527 to daily FTC/TDF, with a primary focus on HIV-1 incidence, safety, and tolerability.
- The program builds on promising Phase II data showing MK-8527’s favorable safety profile and supports global efforts to expand access to long-acting HIV prevention options.
Merck has announced the initiation of the Phase III EXPrESSIVE clinical trial program evaluating the safety and efficacy of MK-8527, an investigational once-monthly, oral nucleoside reverse transcriptase translocation inhibitor for HIV pre-exposure prophylaxis (PrEP).1
Overview of the EXPrESSIVE clinical trial program
The EXPrESSIVE program is comprised of two studies. EXPrESSIVE-11 (MK-8527-011, NCT07044297) will evaluate MK-8527 among people with greater likelihood of HIV-1 exposure with enrollment expected to begin in August 2025. The EXPrESSIVE-10 trial, being conducted in collaboration with the Gates Foundation, will evaluate MK-8527 in women as well as adolescent girls and will begin enrolling in the coming months.
In a press release, Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said: “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. 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.”
Phase II trial supported launch of Phase III program
Merck’s decision to begin this new Phase III program is supported by positive results of a double-blind, multicenter, Phase II trial (MK-8527-007, NCT06045507) investigating the safety and pharmacokinetics of MK-8527. In the study, the rates of adverse events were consistent across both the treatment and placebo arms.
- MK-8527-007 enrolled 350 participants, 18–65 years of age, with low likelihood of HIV-1 exposure
- Participants were randomized 2:2:2:1 to receive MK-8527 (3, 6, or 12 mg) or placebo once monthly for six months
Design and objectives of the EXPrESSIVE trials
Both trials in the EXPrESSIVE program are randomized, active-controlled studies. They will also share the same primary objective of assessing efficacy, safety, and tolerability by comparing the annual incidence of confirmed HIV-1 infections between the two treatment groups. Participants in both studies will receive either once-monthly oral MK-8527 or daily FTC/TDF (emtricitabine/tenofovir disoproxil fumarate).
- In EXPrESSIVE-11, 4,390 sexually active individuals who may benefit from HIV PrEP are expected to be enrolled across 16 countries.
- In EXPrESSIVE-10, 4,580 sexually active women aged 16–30 will be enrolled across Kenya, South Africa, and Uganda.
In the press release, Trevor Mundel, president of global health at the Gates Foundation, added: “Scientific advances against HIV have brought us further than ever imagined and are ushering in a new era in HIV prevention. 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 III trials are a key step toward translating progress into longer-acting options that could help turn the tide on HIV.”
Related progress in HIV treatment with DOR/ISL regimen
The announcement of the Phase III EXPrESSIVE program comes on the heels of the FDA accepting a New Drug Application (NDA) for Merck’s doravirine/islatravir (DOR/ISL) regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. This NDA is based on positive results from two Phase III trials.2
In MK-8591A-052 (NCT05630755), 1.5% of participants who switched to DOR/ISL had a viral load of ≥50 copies/mL at week 48, compared to 0.6% on just bictegravir/emtrictabine/tenofovir alafenamide, meeting the primary endpoint.3
The DOR/ISL regimen also saw success in MK-8591A-051 (NCT05631093), which showed that 1.4% of patients who received DOR/ISL had a viral load of ≥50 copies/mL at week 48, compared to 4.9% on baseline antiretroviral therapy.
References
1. Merck to Initiate Phase 3 Trials for Investigational Once-Monthly HIV Prevention Pill. News release. Merck. July 14, 2025. Accessed July 14, 2025. https://www.businesswire.com/news/home/20250714554719/en/Merck-to-Initiate-Phase-3-Trials-for-Investigational-Once-Monthly-HIV-Prevention-Pill
2. U.S. FDA Accepts New Drug Application for Merck’s Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults with Virologically Suppressed HIV-1 Infection. News release. Merck. July 10, 2025. Accessed July 14, 2024. https://www.businesswire.com/news/home/20250710518672/en/U.S.-FDA-Accepts-New-Drug-Application-for-Mercks-DoravirineIslatravir-an-Investigational-Once-Daily-Oral-Two-Drug-Regimen-for-Treatment-of-Adults-with-Virologically-Suppressed-HIV-1-Infection
3. Doravirine/Islatravir Regimen Shows Promise in Multiple Phase III Trials for the Treatment of HIV. Applied Clinical Trials. March 13, 2025. Accessed July 14, 2025. https://www.appliedclinicaltrialsonline.com/view/doravirine-islatravir-regimen-promise-multiple-phaseiii-trials-treatment-hiv
