Gilead's Novel Capsid Inhibitor Lenacapavir Meets Primary Endpoint in Phase 2/3 Trial for Multidrug-Resistant HIV-1

Compiled by Keke

On November 18, Gilead announced the top-line results from the Phase 2/3 CAPELLA trial, which evaluated the efficacy and safety of lenacapavir, an investigational long-acting HIV-1 capsid inhibitor, in heavily treatment-experienced individuals with multidrug-resistant HIV-1 infection.

The study found that 88% of subjects receiving lenacapavir (n=21/24) achieved at least a 0.5 log10 reduction in HIV-1 viral load at the end of 14 days of functional monotherapy, compared to 17% (n=2/12) in the placebo group. Gilead Sciences expects to share long-term follow-up data from participants in the CAPELLA study next year and plans to submit an application for new drug approval to regulatory authorities based on these data. As part of a long-acting regimen, lenacapavir is used in combination with other antiretroviral drugs for the treatment of HIV-1 infection. If approved, the drug will become the first HIV capsid inhibitor available for the treatment of HIV-1 infection.

In the CAPELLA study, 36 adult patients with multi-class resistant HIV and detectable viral loads after failure of their treatment regimen were randomized in a 2:1 ratio to receive either oral lenacapavir or placebo for 14 days, in addition to continuing their previously failed regimen (functional monotherapy). Among the 24 participants randomized to the lenacapavir group, the median baseline viral load was 4.2 log10 copies/mL, and 67% had CD4 counts below 200 cells/µL. At the end of the 14-day treatment period, the proportion of participants receiving lenacapavir who achieved a reduction in viral load of at least 0.5 log10 copies/mL (the primary endpoint) was statistically significant compared to those receiving placebo added to functional monotherapy (88% vs. 17%, p<0.0001). Furthermore, the mean change in viral load was significantly greater in the lenacapavir group than in the placebo group (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL, p<0.0001).

Furthermore, lenacapavir was generally safe and well tolerated. No serious adverse events related to the study drug were observed during the 14-day period, and no participants discontinued the study drug for any reason, including due to adverse events. The most common adverse events observed in this part of the study included injection site swelling (21%) and injection site nodules (17%), the majority of which were Grade 1 or Grade 2 in severity.

Following a 14-day functional monotherapy period, all subjects entered an open-label study in which lenacavavir was added to the optimized treatment regimen. The CAPELLA study includes a continuous maintenance phase with assessments of subcutaneous lenacavavir administration, as well as the safety and efficacy of lenacavavir and the optimized background regimen, at Weeks 26 and 52.

Initial results from the CAPELLA trial demonstrated that lenacapavir led to a rapid decline in viral load among patients with HIV who had extensive treatment experience and multidrug resistance. This clinical response may have significant implications for both individual patients and public health.

Phase 1 clinical study data presented at the AIDS 2020 conference support the use of lenacapavir administered via subcutaneous injection every six months for the treatment and prevention of HIV. Furthermore, at IDWeek 2020, Gilead announced the addition of a new study arm to evaluate the efficacy of lenacapavir dosed every six months for HIV prevention in women. Additionally, a study is planned for men who have sex with men and transgender individuals, with trials expected to commence in mid-to-late 2021. In May 2019, the U.S. FDA granted Breakthrough Therapy designation to lenacapavir, in combination with other antiretroviral agents, for the treatment of heavily treatment-experienced adults with multidrug-resistant HIV-1 infection.

Reference Source: Gilead’s Lenacapavir Shows Promise for Multidrug-Resistant HIV in Phase II/III Trial

Original Title:Long-Acting Treatment for HIV Infection: Gilead’s Novel Capsid Inhibitor Lenacapavir Meets Primary Endpoint in Phase 2/3 Clinical Trials!