FDA Rejects Gilead’s Drug Application for HIV-1 Treatment

FDA recently issued a complete response letter (CRL) to Gilead rejecting its New Drug Application (NDA) for HIV-1 treatment, lenacapavir.

The agency cited Chemistry Manufacturing and Controls (CMC) issues relating to the compatibility of HIV-1 capsid inhibitor, lenacapavir. FDA previously raised questions regarding vials of borosilicate glass and their compatibility with the lenacapavir solution.

Therefore, FDA placed a clinical hold for lenacapavir in December 2021 due to emerging concerns. The combination of borosilicate glass and lenacapavir could potentially lead to the formation of sub-visible glass particles in the final drug solution. 

During the clinical hold, screening, enrollment, and dosing of study participants were not permitted across any studies. But patient monitoring and dosing of participants in comparator arms continued according to relevant protocol.

Gilead submitted the NDA to the FDA to treat heavily-treatment experienced individuals with multi-drug resistant HIV in June 2021. FDA selected the drug for priority review due to the vast unmet need of this population.

“Gilead intends to provide FDA with a comprehensive plan and corresponding data to use a different vial type. We look forward to discussing this further with FDA over the coming months so that we can make this investigational new therapy available to people living with multidrug-resistant HIV as soon as possible,” Merdad Parsey, MD, PhD, chief medical officer at Gilead, said in the announcement.

Last year, nearly 37.7 million people globally were infected with HIV. Of these, 36 million were adults and 1.7 million were children up to 14 years of age. Lenacapavir would be the only HIV-1 treatment option administered twice a year if FDA-approved.

Gilead supported its NDA submission with 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 optimized antiretroviral background regimen in patients.

At the end of February, the trial found that lenacapavir elicited high rates of virologic suppression and clinically meaningful increases in CD4 counts in patients. Specifically, 83 percent of people with high unmet medical needs who received the combination treatment had an undetectable viral load at week 52. And patients achieved a mean increase in CD4 counts of 83 cells/microliter.