Gilead Sciences, Inc. and Merck announced results from the Phase 2 clinical study evaluating the investigational combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class capsid inhibitor. These late-breaking data were presented during an oral session at the 31st Conference on Retroviruses and Opportunistic Infections (CROI). Prior to the late-breaker oral presentation, the key findings were featured in a CROI press conference.

At 24 weeks, the novel investigational combination maintained a high rate (94.2%) of viral suppression Single-tablet daily oral therapies have helped to transform HIV care, but options that allow for less frequent dosing have the potential to address adherence, stigma and other challenges faced by some individuals taking daily oral antiretroviral therapy. In this open-label, active-controlled study (NCT05052996), virologically suppressed adults (n=104) on Biktarvy®? (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) were randomly located 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. Eighteen% of participants were assigned female at birth, 50% were non-white, and 29% were Hispanic or Latinx. Results of the primary endpoint, measured as HIV-1 RNA 50 copies/mL (c/mL) at Week 24 per FDA Snapshot algorithm, showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of more than 50 copies/mL at Week 24; the participant later suppressed on islatravir and lenACapavir at Week 30.

No participants in the Biktarvy group had a viral load of more of 50 copies/mL at week 24. Results of the secondary endpoint, as measured by the proportion of individuals with HIV-1 RNA < 50 c/mL at Week 24, showed that participants who switched to treatment with once-weekly islatravir and len Acapavir or continued Biktarvy both maintained comparable high rates of HIV suppression at Week 24 (94.2% v. 94.2%). Grade 1 and 2 treatment-related-adverse events (TRAEs) reported in the islatravir and lenacapavir group included dry mouth and nausea (each 3.8%).

No grade 1 and 2 TRAEs were reported in the Biktarvy group. No grade 3 or 4 TRAEs related to study drug in either treatment group were reported. Two participants discontinued islatravir and lenacapavir due to adverse events unrelated to the drug.

In addition, no differences were seen between treatment groups for changes in CD4+ T cell counts or absolute lymphocyte counts. The Phase 2 study will continue in an open-label fashion through Week 48. Longer-term data will be presented at a future scientific conference.

Islatravir, alone or in combination with lenacapavir, is investigational and not approved anywhere globally. The safety and efficacy of the combination of islatravir and lenacapavir have not been established.