Merck Announces Positive Phase 2a Data Supporting Once-Monthly Oral Islatravir for HIV Pre-Exposure Prophylaxis (PrEP)

January 27, 2021/BioValleyBIOON/--Merck & Co. recently at the 2021 HIV Prevention ResearchMeeting(HIVR4P 2021) announced Phase 2aClinical Trial(NCT04003103) New Interim Data. This study is evaluating the safety, tolerability, and pharmacokinetics (PK) of once-monthly oral islatravir (formerly MK-8591) tablets in adults. Interim results indicated that both studied doses (60 mg and 120 mg, administered orally once monthly) for pre-exposure prophylaxis (PrEP) met the prespecified efficacy PK thresholds. In an interim analysis using blinded data, both doses were found to have acceptable tolerability.

Islatravir is a novel oral nucleoside reverse transcriptase translocation inhibitor (NRTTI) under development by MSD, currentlyClinical Trialto evaluate various formulations, in combination with other antiretroviral agents for the treatment of HIV-1 infection, and as monotherapy for pre-exposure prophylaxis (PrEP) against HIV-1 infection.

Dr. Sharon Hillier, the study’s principal investigator and Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of Pittsburgh, stated, “These findings support further research into islatravir as a once-monthly oral PrEP regimen. There is an urgent need for more and more effective HIV prevention options to help a broader population protect themselves.”

Dr. Joan Butterton, Vice President of Global Clinical Development for Infectious Diseases at MSD Research Laboratories, stated: “Despite recognized progress in ending the HIV epidemic, 1.7 million people worldwide were newly infected with HIV in 2019, underscoring the need for greater innovation to alleviate the growing burden of infection. The data we presented at the HIVR4P conference support the evaluation of islatravir as a once-monthly oral PrEP regimen in the Phase 3 IMPOWER trial, which will enroll participants across diverse populations and regions. Our goal is to provide a new strategy for preventing HIV-1 infection among individuals at risk who currently lack available PrEP options.”

In November 2020, Merck Sharp & Dohme (MSD) entered into a collaboration with the Bill & Melinda Gates Foundation, under which the Foundation will provide funding to launch the pivotal Phase 3 study IMPOWER 22 in 2021. This study aims to evaluate once-monthly oral islatravir for pre-exposure prophylaxis (PrEP) among women and adolescent girls at high risk of acquiring HIV-1 infection in sub-Saharan Africa. Currently, more than half of new HIV infections worldwide occur in sub-Saharan Africa, where women account for nearly 60% of new cases in the region.

Chemical Structure of Islatravir (MK-8591) (Image source: medchemexpress.cn)

In an ongoing Phase 2a, randomized, double-blind, parallel-group, placebo-controlled, multicenter trial, participants were randomized (2:2:1) to three once-monthly oral treatment groups: islatravir 60 mg, islatravir 120 mg, or placebo. Participants received monthly treatment with islatravir or placebo during a 24-week blinded treatment period, followed by a 12-week blinded treatment period (after which the sponsor unblinded the study for an interim safety assessment), and a 32-week open-label follow-up in the islatravir groups to characterize the terminal elimination phase. Safety, tolerability, and pharmacokinetic (PK) endpoints were analyzed.

During the interim data analysis, 76.8% (n=192/250) of the planned subjects were randomized to receive treatment. Among these subjects, 32.8% (n=63/192) were male and 67.2% (n=129/192) were female; 30.2% (n=58/192) were Black or African American, and 16.1% (n=31/192) were Hispanic or Latino. In the review of blinded safety data, most adverse events (AEs) were mild or moderate in severity. The most common AEs (reported in >4% of subjects) included headache (7.3%), diarrhea (5.7%), nausea (4.7%), abdominal pain (4.2%), and upper respiratory tract infection (4.2%). Two subjects discontinued treatment due to AEs currently classified as potentially drug-related, including a sensation of a foreign body in the throat (mild) and rash with pruritus (moderate).

Interim pharmacokinetic (PK) analysis of islatravir triphosphate (the active form of islatravir) concentrations in peripheral blood mononuclear cells (PBMCs) indicated that trough concentrations (the lowest levels between doses) following monthly dosing with 60 mg or 120 mg remained above the pre-specified PK threshold of 0.05 pmol/10⁶ PBMCs for HIV-1 prophylaxis. Islatravir PK demonstrated approximately linear dose proportionality at both study doses. Preliminary PK analysis of mucosal tissues (rectal, cervical, and/or vaginal) obtained from a subset of study participants (n=54) indicated rapid and sustained distribution of islatravir in the sampled tissues. Enrollment for this ongoing Phase 2a study has been completed, with the primary analysis of the full dataset expected to be available by late 2021.(BioValley Bioon.com)

Original Source: Merck Presents Interim Findings from Phase 2a Clinical Trial Evaluating Investigational Once-Monthly Oral Islatravir for the Prevention of HIV-1 Infection at HIVR4P 2021