The investigational drug MK-8527 (Merck) was well tolerated in its phase 2 trial presented at IAS 2025, in Kigali, Rwanda.
The study drug could be another option for pre-exposure prophylaxis (PrEP) to patients, said Kenneth Mayer, MD, the medical research director and co-chair of the Fenway Institute and director of HIV Prevention Research at Beth Israel Lahey Health, in Boston. “We all know we’re still seeing too many HIV infections despite many PrEP modalities,” Dr. Mayer said at the conference. Daily oral medication can be a challenge for people, he said, “but some people don’t want to take shots,” he said, referring to long-acting PrEP injectables. In prior research, Dr. Mayer said individuals expressed once-monthly oral PrEP to be a preferred modality.
MK-8527 is a novel oral nucleoside reverse transcriptase translocation inhibitor given once monthly. In the double-blind, multicenter study (ClinicalTrials.gov Identifier: NCT06045507; abstract OAS0106LB), 350 adults at low risk for HIV infection were randomized to receive either 3, 6 or 12 mg of the drug or placebo once monthly for six months. Study participants were an average age of 28 years, more than half identified as female (58.5%) and were predominantly white (51.4%), followed by Black/African American (41.4%) and Asian (2.3%).
The researchers found the incidence of adverse events (AEs) to be similar to placebo (3 mg, 61.4%; 6 mg, 68.3%; 12 mg, 66.7%; placebo, 63.3%). In terms of drug-related AEs, more AEs were seen in the higher than lower doses (3 mg, 14.9%; 6 mg, 15.8%; 12 mg, 20.2%; placebo, 18.4%). Three individuals discontinued the study drug due to AEs: in the 6-mg group, one with migraine and one with decreased lymphocyte/CD4+ count, and one in the 12-mg group with hypoesthesia.
They also found that pharmacokinetic parameters for the study drug were dose proportional (area under the curve: 3 mg, 0.129 h*mcmol/L; 6 mg, 0.404 h*mcmol/L; 12 mg, 0.836 h*mcmol/L; maximum concentration: 3 mg, 0.0320 mcmol/L; 6 mg, 0.0538 mcmol/L; 12 mg, 0.108 mcmol/L; time to maximum concentration: 3 mg, 0.55 hours; 6 mg, 0.56 hours; 12 mg, 0.57 hours).
The results from this study show that MK-8527 should be continued for development, the researchers said. “The study is important because it’s a pathway for clinical development MK-8527 monthly for the prevention of HIV in two upcoming phase 3 studies,” Dr. Mayer said.
Dr. Mayer reported financial relationships with Gilead, Merck and ViiV Healthcare. Merck funded the clinical trial.
