Once Monthly Oral PrEP Medication Will Advance to Phase 3 Study
Investigators find that the phase 2 trial supports the further development of MK-8527 as an HIV pre-exposure prophylaxis.
Investigators will continue to investigate MK-8527, an investigational once monthly oral nucleoside reverse transcriptase translocation inhibitor as HIV pre-exposure prophylaxis (PrEP), in a new phase 3 study, EXPrESSIVE-11 (MK-8527-011; NCT07044297). The decision to initiate a phase 3 trial comes from positive results from a phase 2 trial (MK-8527-007, NCT06045507).1
Investigators find that the phase 2 trial supports the further development of MK-8527 as an HIV pre-exposure prophylaxis. | Image Credit: Bowonpat - stock.adobe.com
“Scientific advances against HIV have brought us further than ever imagined and are ushering in a new era in HIV prevention,” Trevor Mundel, president of global health at the Gates Foundation, said in a news release.1 “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-11 trial, investigators will evaluate the safety and efficacy of the investigational drug with greater likelihood of HIV exposure in 16 countries, which will start enrolling in August 2025. Investigators will also launch the EXPrESSIVE-10 (MK-8527-010) trial, which will evaluate the safety and efficacy of the drug in women and adolescent girls in sub-Saharan Africa.1
Patients included in the EXPrESSIVE-11 trial will have negative HIV test results, be a cisgender man, transgender woman, transgender man, or gender nonbinary person, and weigh 35 kg or more. Treatment included 11 mg MK-8527 once monthly and a placebo to emtricitabine/tenofovir disoproxil fumarate once daily for up to 2 years or active 200 mg emtricitabine/tenofovir disoproxil fumarate once daily and the placebo to MK-8527 once monthly. The primary outcomes included the number of individuals with HIV, the number of patients who experienced at least 1 adverse event (AE), and the number of participants who discontinued the study due to AEs.2
In the phase 2 study, investigators assessed the safety, tolerability, and pharmacokinetics of the oral investigational drug once monthly in individuals at low risk for HIV. Patients received either the low dose, medium dose, or high dose of the drug or the placebo, which were taken once monthly for 6 months and had an 8-week blinded safety follow-up period. The primary outcome included the number of individuals with 1 or more AEs and the number of individuals discontinuing the study due to AEs. Secondary outcomes included the area under the placemat concentration-time curve and the maximum concentration of the drug.3
In the study, 350 patients were enrolled with ages ranging from 18 years to 65 years, and treatment was randomized 2:2:2:1. Investigators found that the rates of adverse events were similar for patients in the study drug groups and those in the placebo arm. Further, they noted that there were no clinically meaningful changes seen in laboratory tests, including total lymphocyte and CD4 T-cell counts. The pharmacokinetics also supported the continued development of the drug as a once monthly option, according to the results from the phase 2 trial.1
READ MORE: HIV Resource Center
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REFERENCES
1. Merck to Initiate Phase 3 Trials for Investigational Once-Monthly HIV Prevention Pill. News release. Merck. July 14, 2025. Accessed July 16, 2025. https://www.merck.com/news/merck-to-initiate-phase-3-trials-for-investigational-once-monthly-hiv-prevention-pill/
2. A Clinical Study of MK-8527 to Prevent Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8527-011). ClinicalTrials.gov identification: NCT07044297. Updated June 29, 2025. Accessed July 16, 2025. https://clinicaltrials.gov/study/NCT07044297
3. Safety and Pharmacokinetic Study of Oral MK-8527 QM in Participants at Low-Risk for HIV-1 Infection (MK-8527-007). ClinicalTrials.gov identification: NCT06045507. Updated March 13, 2025. Accessed July 16, 2025. https://clinicaltrials.gov/study/NCT06045507?term=MK-8527&rank=9
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