Gilead and Merck Begin Phase 2 Trials for Islatravir and Lenacapavir Combination HIV Treatment

The once-weekly regimen of islatravir and lenacapavir is Merck and Gilead’s first clinical trial since collaborating to develop long-acting HIV treatment options.

Gilead Sciences, Inc. and Merck (MSD) announced the commencement of a phase 2 clinical trial to study their investigational HIV treatment regimen. The treatment, a combination of islatravir and lenacapavir, is a once-weekly oral regimen designed for people living with HIV who are virologically suppressed and on antiretroviral therapy (ART).

Gilead and Merck first announced they were joining forces to develop potential long-acting HIV treatment options in March 2021, and Jared Baeten, MD, PhD, Vice President of HIV Clinical Development at Gilead Sciences, spoke highly of their joint efforts. “This innovative research collaboration builds on the efforts of both companies to help make the end of the epidemic a reality through continued scientific advances in HIV. Initiating the trial represents an important step forward toward our goal of offering long-acting options that can help address the differentiated needs and preferences of the diverse range of people living with HIV.”

Islatravir (MK-8591), developed by Merck, and lenacapavir, developed by Gilead, both have long half-lives and have documented activity at low dosages in clinical studies. Creating an HIV regimen that requires less frequent dosing is an important step toward making HIV treatment more readily available and accessible.

The phase 2 study, NCT05052996, will evaluate the antiviral effect of an oral weekly regimen of Gilead’s investigational capsid inhibitor, lenacapavir, and Merck’s investigational nucleoside reverse transcriptase translocation inhibitor, islatravir. NCT05052996 is an open-label, active-controlled, multicenter study that will enroll adults 18 years of age and older at 25 sites in the US.

75 patients who meet all eligibility requirements will be randomly allocated 2:1; treatment group 1 will receive oral weekly islatravir (20 mg) and lenacapavir (300 mg) on day 8 after receiving loading doses of islatravir (40 mg) and lenacapavir (600 mg) on days 1 and 2. Treatment Group 2 will receive oral daily B/F/TAF (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets). Participants will receive the investigational drugs for 48 weeks. The primary endpoint the proportion of study participants with HIV-1 RNA viral load greater than or equal to 50 c/mL at Week 24.

After completion of the 48-week trial, participants in Treatment Group 1 will continue to receive an oral weekly combination regimen of islatravir and lenacapavir. They will be reevaluated every 12 weeks. Treatment Group 2 will be switched from daily oral B/F/TAF tablets to the oral weekly combination of islatravir and lenacapavir, beginning with the 2 days of loading doses, and monitored every 12 weeks.