Gilead Resubmits NDA of Long-Acting Lenacapavir for HIV

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

Gilead Sciences has resubmitted its new drug application (NDA) to FDA for lenacapavir for the treatment of patients with HIV-1 infection in heavily treatment-experienced patients.

“There are people with HIV who have severely limited treatment options due to resistance to multiple antiretroviral therapy classes,” Jared Baeten, M.D., Ph.D., vice president, HIV clinical development, Gilead Sciences, said in a press release.

In February 2022, the FDA had issued a complete response letter (CRL) for lenacapavir, citing 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.

The resubmission contains CMC data to support the compatibility of lenacapavir with an alternative vial type made from aluminosilicate glass

The NDA is supported by data from the phase 2/3 CAPELLA study, which evaluated the antiviral activity of lenacapavir administered every six months as a subcutaneous injection. The trial showed that, based on week 26 data, lenacapavir achieved high rates of virologic suppression in heavily treatment-experienced people with HIV.

Lenacapavir is a first-in-class, investigational long-acting HIV-1 capsid inhibitor. s designed to inhibit HIV-1 at multiple stages of its lifecycle and has no known cross resistance to other existing drug classes. If approved, lenacapavir would be the only HIV-1 treatment option administered twice-yearly.

Data on lenacapavir presented at the 29th Conference on Retroviruses and Opportunistic Infections from the CAPELLA trial. The data were also published in May 2022 by the New England Journal of Medicine.

The trial 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 in people living with HIV whose virus was no longer effectively responding to their current therapy. In the CAPELLA study, the most common adverse events observed were injection site reactions (63%), nausea and diarrhea (13% each), and COVID-19 (11%).

In Europe, lenacapavir recently received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The CHMP positive opinion will be reviewed by the European Commision, which has the authority to authorize medicines in the 27 Member States of the European Union, as well as Norway, Iceland and Liechtenstein. The final European Commission decision is expected later this year.