Gilead Submits New Drug Application for Lenacapavir for the Treatment of HIV

A new drug application for the investigational therapy lenacapavir has been submitted to the FDA for the treatment of HIV-1 infection in heavily treatment-experienced people with multi-drug-resistant infection, according to a press release from Gilead.

The submission is supported by data from the phase 2/3 CAPELLA trial, which evaluated the safety and efficacy of lenacapavir administered subcutaneously every 6 months in combination with an antiretroviral background regimen. Key data will be presented during the 11th International AIDS Society Conference in July.

Lenacapavir was granted Breakthrough Therapy Designation in May 2019 and is a potential first-in-class capsid inhibitor for the treatment of HIV-1 infection without overlapping resistance with any currently approved antiretroviral therapy. It is being developed in combination with other antiretroviral agents for the treatment of both adults and pediatric patients weighing at least 35 kg with MDR HIV-1 infection who are currently on a failing antiretroviral treatment regimen due to resistance, intolerance, or safety considerations.

“Lenacapavir is an important breakthrough innovation with the potential to be transformative for people living with multi-drug resistant HIV who have very limited treatment options,” said Merdad Parsey, MD, PhD, chief medical officer of Gilead Sciences, in the press release.

CAPELLA is a phase 2/3, double-blinded, placebo-controlled global multicenter study including men and women living with HIV-1. According to the press release, 36 participants with multi-class HIV-1 drug resistance and a detectable virus load while on a failing regimen were randomly allocated to receive oral lenacapavir or placebo for 14 days, in addition to continuing their failing regimen.

The primary endpoint was the proportion of participants in the lenacapavir group who achieved 0.5 log10 copies/mL or more reduction from baseline in HIV-1 RNA at the end of the functional monotherapy period. The study achieved this endpoint by demonstrating that a significantly higher proportion of participants randomly allocated to receive lenacapavir achieved a clinically meaningful viral load reduction from baseline compared with those receiving placebo.

Specifically, those in the lenacapavir arm saw a mean decrease in viral load of -1.93 log10 copies/mL, compared to a mean decrease of -0.29 in the placebo arm. Lenacapavir was generally well-tolerated, with no serious adverse events related to treatment and no study drug discontinuations through the 14-day period.

Following the 14-day functional monotherapy period, participants in the lenacapavir arm started open-label lenacapavir and an optimized background regimen, whereas those enrolled in a separate treatment cohort received open-label lenacapavir and an optimized background regimen on day 1. This maintenance period is evaluating the additional trial endpoints of safety and efficacy and is ongoing.

Lenacapavir is designed to inhibit HIV-1 replication by interfering with multiple steps of the viral lifecycle, including capsid-mediated uptake of HIV-1 proviral DNA, virus assembly and release, and capsid core formation, according to the press release. It is not yet approved for any use and its safety and efficacy are not established.

“The filing moves us one step closer to providing an innovative treatment option that helps to address barriers to achieving viral suppression and meet the unmet needs of people living with multi-drug resistant HIV,” Parsey concluded in the press release.

REFERENCE

Gilead Submits New Drug Application to US Food and Drug Administration for Lenacapavir, an Investigational, Long-Acting Capsid Inhibitor for the Treatment of HIV-1 in People With Limited Therapy Options. News release. Gilead Sciences. June 28, 2021. Accessed June 29, 2021. https://www.gilead.com/news-and-press/press-room/press-releases/2021/6/gilead-submits-new-drug-application-to-us-food-and-drug-administration-for-lenacapavir-an-investigational-longacting-capsid-inhibitor-for-the-tre