Clinical Trial Shows Safety, Efficacy of Monthly Oral Islatravir for HIV-1 Prevention

Six monthly oral doses of islatravir (Merck), an investigational nucleoside reverse transcriptase translocation inhibitor, were generally well tolerated versus placebo for pre-exposure prophylaxis (PrEP) of HIV-1 infection in adults at low-risk of contracting HIV-1, according to the results of an ongoing phase 2a clinical trial presented at the virtual 11th International AIDS Society Conference on HIV Science.

The investigators noted that the levels of islatravir in peripheral blood mononuclear cells (PBMCs) remained above the efficacy pharmacokinetics (PK) threshold for PrEP for both doses studied (60 mg and 120 mg) for 8 weeks following the last study dose.

Islatravir is currently being evaluated in clinical trials for the treatment of HIV-1 infection in combination with other antiretrovirals, as well as for use as PrEP of HIV-1 infection as a single agent. The ongoing phase 2a trial—a randomized, double-blind, parallel assignment, placebo-controlled, multicenter study of adults at low-risk for acquiring HIV-1 infection—assigned participants to 1 of 3 groups in a 2:2:1 ratio.

These groups each received once-monthly oral therapy over a 24-week blinded therapy period, either of islatravir 60 mg, islatravir 120 mg, or placebo. This was followed by a 12-week blinded follow-up for all groups and a 32-week unblinded follow-up for the islatravir groups to identify the terminal elimination phase.

At the time of analysis, unblinded safety data showed that both doses of islatravir were generally well tolerated versus placebo over 24 weeks and most adverse events (AEs) were mild, according to the investigators. No serious drug-related AEs were observed in participants receiving islatravir. PK analysis demonstrated that the lowest level concentrations between doses of islatravir triphosphate in PBMCs following either dosage level remained above the pre-specified PK threshold for HIV-1 prophylaxis of 0.05 pmol/106 PBMCs. These levels were sustained through 8 weeks following the final dose.

“The 24-week analysis of investigational, once-monthly oral islatravir not only builds upon the PK data we have already seen, but also provides encouraging support for the safety and tolerability profile of this HIV-1 PrEP regimen,” said Joan Butterton, MD, vice president of global clinical development for infectious diseases at Merck Research Laboratories, in a press release. “As part of our commitment to understanding the potential for our HIV medicines in a broad range of patients, we focused on the enrollment of diverse patient populations at risk for HIV, including women, who have one of the highest unmet needs in HIV prevention.”

REFERENCE

Merck Presents New Data from Ongoing Phase 2a Clinical Trial Evaluating the Safety, Tolerability and Pharmacokinetics of Investigational, Once-Monthly, Oral Islatravir for HIV-1 Prevention at IAS 2021 [news release]. Merck; July 20, 2021. Accessed July 23, 2021. https://www.merck.com/news/merck-presents-new-data-from-ongoing-phase-2a-clinical-trial-evaluating-the-safety-tolerability-and-pharmacokinetics-of-investigational-once-monthly-oral-islatravir-for-hiv-1-prevention-at-ias-2021/