FDA Issues Complete Response Letter for Long-Acting HIV Therapy

The FDA cited issues related to the compatibility of lenacapavir and the vial used. The agency has not requested new clinical studies.

Gilead Sciences has received a complete response letter (CRL) for the new drug application (NDA) for lenacapavir, an investigational, long-acting HIV-1 capsid inhibitor under review for the treatment of HIV-1 infection in heavily treatment-experienced people with multi-drug resistant HIV-1 infection.

In the CRL, the FDA has cited chemistry manufacturing and controls (CMC) issues relating to the compatibility of lenacapavir with the proposed container vial. In December 2021, the FDA had placed a clinical hold on trials with lenacapavir. The agency had raised questions about vials made of borosilicate glass and their compatibility with lenacapavir solution. The concern was about the possibility of glass particles forming in the solution of lenacapavir.

Company officials say they are working with the FDA on a plan for a different vial.

The lenacapavir NDA was submitted in June 2021 and selected for priority review because of the significant unmet need for treatments for patients with multi-drug resistant HIV. The submission was based on data from the phase 2/3 CAPELLA trial, which evaluated the safety and efficacy of lenacapavir administered subcutaneously every six months in combination with an antiretroviral background regimen in heavily treatment-experienced people with multi-drug resistant HIV-1 infection.

This study found that a higher proportion of participants randomly allocated to receive lenacapavir achieved a clinically meaningful viral load reduction from baseline compared with those receiving placebo during the 14-day functional monotherapy period.

In February 2022, the company released new data that showed that lenacapavir, administered subcutaneously every six months in combination with other antiretrovirals, achieved high rates of virologic suppression and clinically meaningful increases in CD4 counts.

If approved, lenacapavir would be the first HIV-1 treatment administered twice yearly.