FDA Lifts Clinical Hold on Lenacapavir for HIV Treatment and PrEP

The FDA previously placed a clinical hold on lenacapavir in borosilicate vials in all clinical studies because of emerging concerns about the compatibility of vials made of borosilicate glass.

The FDA has lifted a clinical hold placed on Gilead Sciences’ Investigational New Drug Application for injectable lenacapavir for HIV treatment and pre-exposure prophylaxis (PrEP).

In December 2021, the FDA placed the clinical hold on lenacapavir in borosilicate vials in all clinical studies because of emerging concerns about the compatibility of vials made of borosilicate glass with lenacapavir solution. This compatibility issue could potentially cause the formation of sub-visible glass particles in the solution of lenacapavir, according to the FDA.

However, oral formulation dosing of lenacapavir continued according to the relevant study protocol as the FDA evaluated corresponding data on the storage and compatibility of lenacapavir injection with an alternative vial made from aluminosilicate glass.

“We are pleased to have identified an alternative vial for lenacapavir, and to now advance the robust clinical program for this potential first-in-class long-acting option for HIV treatment and prevention,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, in a press release. “[This] news brings us one step closer to our goal of offering therapeutic options for the diverse communities affected by HIV as we work to end the epidemic for everyone, everywhere.”

Lenacapavir is a potential first-in-class, investigational long-acting HIV-1 capsid inhibitor being developed for the treatment and prevention of HIV-1 infection. The multi-stage mechanism of action for the drug is distinguishable from currently approved antiviral drug classes and is intended to provide a new avenue to develop long-acting treatments for individuals infected with, or at risk for, HIV-1, according to Gilead.

In May 2019, the FDA granted lenacapavir with Breakthrough Therapy Designation for the treatment of HIV infection in heavily treatment-experienced patients with multi-drug resistance in combination with other antiretroviral drugs. Although most antiretroviral agents act on just 1 stage of viral replication, lenacapavir targets multiple stages of the HIV-1 lifecycle and has no known cross resistance to other existing drug classes, according to Gilead. If approved, lenacapavir would be the only HIV-1 treatment option administered twice a year.

All activity in clinical studies analyzing injectable lenacapavir for HIV treatment and HIV PrEP can now continue. Gilead said it will work with study site investigators to fully resume the lenacapavir clinical development programs as soon as possible.

The safety, efficacy, and dosing of lenacapavir are being evaluated in multiple ongoing clinical studies, including CAPELLA, a phase 2/3, double-blinded, placebo-controlled global multicenter study. Results from the 2/3 CAPELLA trial in heavily treatment-experienced individuals with multi-drug resistant HIV showed that lenacapavir administered subcutaneously every 6 months in combination with other antiretrovirals achieved clinically meaningful increases in CD4 counts and high rates of virologic suppression for this population.

In addition to high rates of viral suppression, individuals in the CAPELLA study achieved a mean increase in CD4 count of 83 cells/µL. The trial met its primary endpoint by demonstrating that a significantly higher proportion of individuals randomized to receive lenacapavir achieved a clinically meaningful vial load reduction of at least 0.5 log10 copies/mL during the 14-day functional monotherapy period.

Patients administered lenacapavir achieved a statistically significant greater mean decrease in viral load than those who received the placebo during the functional monotherapy period. Investigators found that lenacapavir was well tolerated with 1 adverse event (AE) leading to the discontinuation at week 52, and no serious AEs were related to lenacapavir.

The most common AE observed to date was injection site reactions, which were mostly mild or moderate.

Reference

FDA Lifts Clinical Hold on Investigational Lenacapavir for the Treatment and Prevention of HIV. Gilead Sciences. News release. May 16, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/5/fda-lifts-clinical-hold-on-investigational-lenacapavir-for-the-treatment-and-prevention-of-hiv