Gilead, Merck launch Phase II trial evaluating oral regimen for HIV-1 treatment
Gilead Science and Merck (known as MSD outside the boundaries of the US and Canada) have announced the initiation of a Phase II study intended to evaluate an investigational, once-weekly oral combination regiment of islatravir and lenacapavir in people living with HIV who are virologically suppressed on antiretrovirals.
According to Jared Baeten, vice president of HIV clinical development with Gilead, partnerships like this between companies are “critical” to continuing to advance solutions that could end the HIV epidemic.
“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,” Baeten commented. “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.”
The Merck-Gilead collaboration (first announced in March) reportedly constitutes an effort by the two companies to build upon their accumulated efforts to advance HIV care by centering on long-acting therapies.
“The initiation of this study is key to further understanding the potential of islatravir and lenacapavir in combination for the treatment of HIV-1, and demonstrates Merck and Gilead’s shared commitment to address the unmet needs of people living with HIV and to contribute to global efforts to end the pandemic,” said Joan Butterton, vice president of global clinical development for infectious diseases, with Merck Research Laboratories.
According to the partners, both of the drugs have shown to possess long half-lives and have demonstrated activity at low dosages in independent clinical studies, supporting the development as an investigational oral or injectable combination regimen with long-acting formulations. Daily single-tablet oral regimens currently are available for people living with HIV; however, oral or injectable regimen options that allow for less frequent dosing reportedly have the potential to address preference considerations, as well as issues associated with stigma, adherence, and privacy.
The Phase II study reportedly is designed to evaluate the safety and antiviral effect of an oral weekly regimen of Merck’s investigational nucleoside reverse transcriptase translocation inhibitor, islatravir, in combination with Gilead’s investigational capsid inhibitor, lenacapavir. The primary endpoint is the proportion of study participants with HIV-1 RNA viral load ≥ 50 c/mL at Week 24.
Lenacapavir and islatravir, alone and in combination, are investigational and not approved anywhere globally. Their safety and efficacy have not yet been established. Further, there is currently no cure for HIV or AIDS.
Patient participants 18 years and older are to be enrolled in this study, which is being conducted at 25 sites in the United States. In the study, 75 participants meeting eligibility criteria will be randomly allocated in a 2:1 ratio to receive oral weekly islatravir (20 mg) administered with oral lenacapavir (300 mg) on day 8 following a loading dose of islatravir (40 mg) and lenacapavir (600 mg) on days 1 and 2 or oral daily B/F/TAF (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets). Participants will receive study drugs for 48 weeks.
After wrapping up the 48th-week visit, patients in Treatment Group 1 will continue to receive an oral weekly regimen of islatravir in combination with oral lenacapavir and be evaluated every 12 weeks. Participants in the second group will switch from daily oral B/F/TAF tablets to an oral weekly regimen of islatravir in combination with oral lenacapavir (starting with the loading doses over 2 days) and continue the study with visits every 12 weeks thereafter.