Gilead and Merck's Phase 2 Data: Weekly Islatravir-Lenacapavir Regimen Maintains Viral Suppression at 48 Weeks

On October 19, 2024, Gilead Sciences, Inc. and Merck announced the promising results from a Phase 2 clinical study examining a novel combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-of-its-kind HIV-1 capsid inhibitor. These findings were shared at the ID Week 2024 conference held in Los Angeles and virtually from October 16-19.

The study, which ran for 48 weeks, showed that 94.2% of participants (n=49) who were virologically suppressed remained with HIV-1 RNA levels below 50 copies/mL. Notably, no participants had viral loads of 50 copies/mL or higher at the 48-week mark. Initial results at 24 weeks, including the primary endpoint, were previously reported at the 31st Conference on Retroviruses and Opportunistic Infections (CROI).

Dr. Jared Baeten, Senior Vice President of Virology Therapeutic Area Head at Gilead Sciences, emphasized the importance of person-centered HIV treatment options. He mentioned that the complexities of HIV care necessitate a variety of options tailored to the needs and preferences of those affected by the virus. The data presented at ID Week reflect Gilead's dedication to ongoing scientific discovery aimed at transforming HIV treatment.

In the open-label, active-controlled study (NCT05052996), virologically suppressed adults (n=104) previously on Biktarvy® were randomized to either receive weekly oral doses of islatravir and lenacapavir (n=52) or continue their daily Biktarvy regimen (n=52). Participants' median age was 40 years, with 18% assigned female at birth, 50% non-white, and 29% Latine.

The results showed comparable high rates of HIV suppression between those who switched to the weekly regimen (94.2%) and those who continued daily Biktarvy (92.3%). No participants in either group exhibited a viral load of 50 copies/mL or higher at week 48.

The study found that 19.2% of participants in the islatravir and lenacapavir group experienced treatment-related adverse events (TRAEs), the most common being dry mouth and nausea (each at 3.8%). In the Biktarvy group, 5.8% reported TRAEs. No serious grade 3 or 4 TRAEs were observed in either group. Two participants discontinued the islatravir and lenacapavir treatment due to unrelated adverse events. There were no significant differences in mean changes from baseline in CD4+ T-cell counts or absolute lymphocyte counts between the treatment groups, and no participants discontinued due to decreases in these counts.

Dr. Elizabeth Rhee, Vice President of Global Clinical Development at Merck Research Laboratories, noted that daily single-tablet regimens, though transformative, can be difficult for some to maintain. She highlighted the potential of less frequent dosing options, like the once-weekly regimen, in supporting adherence and reducing stigma. The encouraging 48-week data support the advancement to phase 3 clinical trials in collaboration with Gilead.

The promising antiviral activities and pharmacokinetic profiles of islatravir and lenacapavir back their continued development as a once-weekly oral combination regimen for virologically suppressed HIV patients. This combination is being further explored in two Phase 3 studies (NCT06630286 and NCT06630299).

Islatravir and lenacapavir remain investigational and are not approved anywhere globally. The safety and efficacy of this combination have yet to be established. Lenacapavir is currently under investigation in several early and late-stage development programs, potentially offering diverse person-centric treatment options for those living with HIV and benefitting from pre-exposure prophylaxis (PrEP).

Gilead and Merck continue to seek innovative solutions to meet the evolving needs of people with HIV, aiming to transform HIV into a manageable and preventable condition through ongoing research and development.