Combination Investigational HIV Therapy Shows Viral Suppression in Adults at Week 48
The late-breaking ID Week session reported on the once-weekly oral regimen being studied for use in people with HIV who are virologically suppressed.
Image credit: Cottonbro, Pexels
Gilead and Merck released their Week 48 results from their phase 2 clinical study which evaluated their investigational combination regimen of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class capsid inhibitor, as an investigational long-acting, once-weekly treatment in people with HIV who are virologically suppressed on antiretroviral therapy.
This was presented as a late-breaking session at IDWeek 2024.
“Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain. Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy,” said Elizabeth Rhee, MD, vice president, Global Clinical Development, Merck Research Laboratories. “We are pleased to see these encouraging 48-week data for this once-weekly oral combination regimen and advance to phase 3 clinical trials in collaboration with Gilead.”
The 2 companies are partnering on the combination therapy. It is important to note, Islatravir, alone or in combination with lenacapavir, is investigational and not approved anywhere globally.
Study Specifics
In this open-label, active-controlled study, virologically suppressed adults (n=104) on Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) were randomly allocated in a 1:1 ratio to receive either oral islatravir 2 mg and lenacapavir 300 mg once a week (n=52) or to continue daily oral Biktarvy (n=52). The median age of participants was 40 years (20-76). Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Latine.2
The proportion of individuals with HIV-1 RNA <50 c/mL at Week 48 by FDA snapshot algorithm (a secondary endpoint), showed that participants who switched to treatment with once-weekly islatravir and lenacapavir (ISL + LEN) or continued Biktarvy maintained comparable high rates of HIV suppression at Week 48 (94.2% v. 92.3%, respectively). No participants treated with either ISL + LEN or Biktarvy had a viral load of ≥ 50 copies/mL at Week 48 (another secondary endpoint).2
Treatment-related-adverse events (TRAEs), as attributed by study investigator, were experienced by 19.2% of participants (n=10/52) in the ISL + LEN group and the most common were dry mouth (n=2/52; 3.8%) and nausea (n=2/52; 3.8%). TRAEs were reported by 5.8% of participants in the Biktarvy group (n=3/52). No grade 3 or 4 TRAEs related to the study drug were reported in either treatment group. Two participants (n=2/52; 3.8%) discontinued ISL + LEN due to adverse events unrelated to the drug. At Week 48 no significant differences were seen between treatment groups in mean change from baseline in CD4+ T-cell counts or absolute lymphocyte counts. No participants discontinued due to a decrease in CD4+ T-cell or lymphocyte counts.2
This investigational combination of weekly oral ISL 2 mg + LEN 300 mg is being further evaluated as a fixed-dose combination regimen in 2 phase 3 studies in virologically suppressed people with HIV. Gilead and Merck are committed to collaborating on the development of this potential once-weekly oral therapy option for people with HIV.
“The future of HIV treatment is person-centered, with long-acting options tailored to help meet the needs and preferences of people affected by HIV,” said Jared Baeten, MD, PhD, senior vice president, Virology Therapeutic Area head, Gilead Sciences. "There is no ‘one size fits all’ approach. The complexities of HIV care require putting people first in the development of biomedical innovations as we keep striving to offer options for all those living with HIV.1
