Once-Monthly Oral Islatravir Shows Promising Results in Phase 2a Trial for HIV-1 Pre-Exposure Prophylaxis (PrEP): Zero Infections Over Six Months
Jul 21, 2021 02:41
CST Updated
02:41
MSD
Pharmaceutical R&D and Manufacturer
July 21, 2021 /Bio ValleyBIOON/ -- MSD (Merck & Co.) recently at the 11th International AIDS Society (IAS) HIV ScienceConferenceShangshang announced Phase 2aClinical Trialresults of (NCT04003103). This study is evaluating:Over a 24-week (6-month) period, once-monthly oral islatravir (formerly MK-8591, tablets) for HIV-1 pre-exposure prophylaxis (PrEP) in adults at low risk of HIV-1 infectionSafety, Tolerability, and Pharmacokinetics (PK).
islatravir is an investigational drug from MSDNovel oral nucleoside reverse transcriptase translocation inhibitor (NRTTI), various dosing regimens are currently being evaluated in clinical trials, including in combination with other antiretroviral agents for the treatment of HIV-1 infection, and as monotherapy for the prevention of HIV-1 infection (i.e., pre-exposure prophylaxis, PrEP). The islatravir clinical program currently includes six Phase 3Clinical Trial，including two Phase 3 IMPOWER trials (IMPOWER-22, IMPOWER-24) evaluating islatravir as a once-monthly oral PrEP regimen in diverse populations who may benefit from additional HIV-1 prevention options.
The Phase 2a trial results presented at the meeting showed that, after 24 weeks of treatment, once-monthly oral islatravir compared with placebo,`Overall tolerability was good`，No subjects experienced confirmed HIV infection.。Most adverse events (AEs) were mild. No serious drug-related adverse events occurred in subjects receiving islatravir. At the 2 study doses (60 mg and 120 mg),Eight weeks after the last study dose, islatravir levels in peripheral blood mononuclear cells (PBMCs) remained above the prespecified efficacy pharmacokinetic (PK) threshold for PrEP.。
Islatravir (MK-8591) Chemical Structure (Image Source: medchemexpress.cn)
Despite recognized progress in ending the HIV epidemic, there were still 1.7 million new HIV infections globally in 2019, highlighting the need for further innovations to alleviate the growing infection burden. These results, presented at the conference, support further investigation of islatravir as a once-monthly oral PrEP regimen. There is an urgent need for additional and more effective HIV prevention options to help protect a broader population.
Dr. Joan Butterton, Vice President of Global Clinical Development for Infectious Diseases at MSD Research Laboratories, said: “The 24-week analysis of 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 of this HIV-1 PrEP regimen. As part of our commitment to understanding the potential of our HIV medicines across a broad patient population, we are focusing on enrolling diverse populations at risk of HIV infection, including women, who have the highest unmet need in HIV prevention.”
Islatravir Clinical Development Program
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 oral islatravir or placebo once monthly during a 24-week blinded treatment period, followed by a 12-week blinded follow-up for all groups and a 32-week unblinded follow-up for the islatravir groups to characterize the terminal elimination phase. Safety, tolerability, and pharmacokinetics (PK) will be assessed through Week 68.
In this 24-week analysis (end of the study dosing period), of the 242 randomized participants, 92% (n=222/242) completed dosing, and 8% (n=20/242) discontinued the study intervention prior to Week 24. Less than 1% (n=2) discontinued treatment due to adverse events (AEs). Among all participants, 67.4% (n=163/242) were female, 52.9% (n=128/242) were White, 41.7% (n=101/242) were Black or African American, and 14.9% (n=36/242) were Hispanic or Latino.
Unblinded safety data indicate that,Compared with placebo, both doses of islatravir were generally well tolerated over 24 weeks, with most adverse events being mild (73.5%).. The most common adverse events (incidence >5%) in the islatravir 60 mg group, islatravir 120 mg group, and placebo group were headache (10.3% [n=10/97], 9.3% [n=9/97], and 4.2% [n=2/48]), diarrhea (5.2% [n=5/97], 5.2% [n=5/97], and 8.3% [n=4/48]), and nausea (5.2% [n=5/97], 7.2% [n=7/97], and 4.2% [n=2/48]).No serious drug-related adverse events were observed in the population receiving islatravir treatment.
This study enrolled a population at low risk of HIV infection,During treatment, no subjects experienced confirmed HIV infection.. PK analysis demonstrated that following once-monthly oral doses of 60 mg or 120 mg, the trough concentration (the lowest level between doses) of islatravir triphosphate in peripheral blood mononuclear cells (PBMCs) continued to remain above the pre-specified pharmacokinetic (PK) threshold for HIV-1 prevention of 0.05 pmol/10^6 PBMCs, and was sustained for 8 weeks following the last dose of islatravir. (Bioon.com)