Gilead and Merck Report Promising Phase 2 Results for Once-Weekly HIV Combination Therapy
核心洞察
Gilead and Merck (搜索) announced Phase 2 data showing their investigational once-weekly oral combination of islatravir and lenacapavir maintained 94.2% viral suppression at 24 weeks in HIV (搜索) patients.
The study enrolled 104 virologically suppressed adults who were randomized to receive either the weekly combination or continue daily Biktarvy treatment, with comparable efficacy between groups.
Only one participant (1.9%) in the weekly treatment group had detectable viral load above 50 copies/mL at week 24, but later achieved suppression by week 30.
Gilead Sciences and Merck (搜索) have reported encouraging Phase 2 results for their investigational once-weekly oral HIV (搜索) treatment combining islatravir and lenacapavir, marking a significant step toward less frequent dosing options for HIV patients. The data, presented at the 31st Conference on Retroviruses and Opportunistic Infections (CROI), demonstrated that the combination maintained high rates of viral suppression comparable to daily therapy.
Study Design and Patient Population
The open-label, active-controlled study (NCT05052996) enrolled 104 virologically suppressed adults currently taking Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). Participants were randomly allocated in a 1:1 ratio to receive either oral islatravir 2 mg and lenacapavir 300 mg once weekly (n=52) or continue daily Biktarvy (n=52).
The study population had a median age of 40 years, with 18% assigned female at birth, 50% non-white, and 29% Hispanic or Latinx participants, reflecting diversity in the HIV (搜索) treatment landscape.
Efficacy Results
At 24 weeks, the primary endpoint results showed that only one participant (1.9%) in the islatravir and lenacapavir group had a viral load above 50 copies/mL, compared to zero participants in the Biktarvy control group. Notably, this participant later achieved viral suppression by week 30 while continuing the weekly regimen.
The secondary endpoint demonstrated that both treatment groups maintained comparable high rates of HIV (搜索) suppression at week 24, with 94.2% of participants in both the weekly combination and daily Biktarvy groups achieving HIV-1 RNA levels below 50 copies/mL.
Safety Profile
The weekly combination demonstrated a favorable safety profile. Grade 1 and 2 treatment-related adverse events in the islatravir and lenacapavir group included dry mouth and nausea, each occurring in 3.8% of participants. No grade 1 or 2 treatment-related adverse events were reported in the Biktarvy group.
Importantly, no grade 3 or 4 treatment-related adverse events were reported in either treatment group. Two participants discontinued the weekly combination due to adverse events unrelated to the study drugs. Additionally, no differences were observed between treatment groups for changes in CD4+ T cell counts or absolute lymphocyte counts.
Clinical Significance
"HIV (搜索) treatment is not one size fits all – developing once-weekly treatment options could help meet the needs of each individual, aiming toward maximizing long-term outcomes for people with HIV," said Dr. Jared Baeten, Vice President of HIV Clinical Development at Gilead Sciences.
The development addresses key challenges in HIV (搜索) care, as single-tablet daily oral therapies have transformed treatment but options allowing less frequent dosing could help address adherence, stigma, and other challenges faced by individuals taking daily antiretroviral therapy.
Dr. Elizabeth Rhee, vice president of global clinical development at Merck (搜索) Research Laboratories, emphasized the collaborative commitment: "Our strategies for managing and treating HIV (搜索) must evolve with the needs of the HIV community and we are excited to have these promising first data from the Phase 2 study."
Drug Development Context
Islatravir is Merck (搜索)'s investigational nucleoside reverse transcriptase (搜索) translocation inhibitor, while lenacapavir is Gilead's first-in-class capsid (搜索) inhibitor. Lenacapavir, marketed as Sunlenca, is already approved in multiple countries for treating multi-drug resistant HIV (搜索) in combination with other antiretrovirals and represents the only HIV treatment administered twice-yearly.
The potent antiviral activities and pharmacokinetic profiles of both compounds support their development as a once-weekly oral combination. Lenacapavir's multi-stage mechanism of action distinguishes it from other approved antiviral classes, as it inhibits HIV (搜索) at multiple stages of its lifecycle with no known cross-resistance to existing drug classes.
Future Development
The Phase 2 study will continue in an open-label fashion through week 48, with longer-term data to be presented at future scientific conferences. Both islatravir alone and in combination with lenacapavir remain investigational and are not approved anywhere globally.
This development represents part of Gilead's broader strategy to develop lenacapavir as a foundation for future HIV (搜索) therapies, offering both long-acting oral and injectable options with various dosing frequencies. The approach aims to address individual needs and preferences of people with HIV and those who could benefit from pre-exposure prophylaxis.