Gilead Resubmits NDA for Lenacapavir, Updates Based on FDA Complete Response Letter

Gilead Sciences announced the resubmission of a new drug application (NDA) to the FDA for lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced individuals with multi-drug resistant HIV-1 infection.¹

Lenacapavir is an investigational, long-acting HIV-1 capsid inhibitor that has yet to be approved by any regulatory authority for any use and its safety and efficacy are not established.¹

"There are [individuals] with HIV who have severely limited treatment options due to resistance to multiple antiretroviral therapy classes," Jared Baeten, MD, PhD, vice president of HIV Clinical Development at Gilead Sciences, said in a statement. "We are committed to addressing unmet needs and recognize the urgency for filling the critical treatment gap for people with multi-drug resistant HIV whose virus is no longer effectively responding to their current therapy."¹

Gilead resubmitted the NDA in response to the FDA Complete Response Letter (CRL) issued in February 2022, which cited chemistry manufacturing and control (CMC) issues relating to the compatibility of lenacapavir in borosilicate vials as the reason for the FDA action.¹

In December 2021, the FDA 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 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.

In May, the FDA lifted a clinical hold placed on injectable lenacapavir for HIV treatment and pre-exposure prophylaxis. 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.

The NDA resubmission contains comprehensive CMC data to support the compatibility of the drug with an alternative vial type made from aluminosilicate glass.¹

Additionally, the NDA is supported by extensive pre-clinical and earlier clinical research data, as well as data from the phase 2/3 CAPELLA study. The CAPELLA study evaluated the antiviral activity of lenacapavir administered every 6 months as a subcutaneous injection, in combination with other antiretrovirals in individuals with multi resistant HIV-1 infection.¹

Once excepted by the FDA, a new PDUFA will be established for lenacapavir.¹

The original NDA was submitted to the FDA in June 2021 and selected for priority review due to the significant unmet need for this population. The submission was also supported by data from the CAPELLA trial.

The clinical data on lenacapavir were also presented at the 29th Conference on Retroviruses and Opportunistic Infections (Virtual CROI 2022).²

The week 52 findings from the CAPELLA trial demonstrated that lenacapavir, which was administered subcutaneously every 6 months in combination with other antiretrovirals, achieved high rates of virologic suppression and clinically meaningful increases in CD4 counts in individuals living with HIV whose virus was no longer effectively responding to their current therapy.²

The most common adverse events that were observed in the CAPELLA study were injection site reactions, nausea, diarrhea, and COVID-19.²

Reference

1. Gilead resubmits new drug application to US Food and Drug Administration for lenacapavir, an investigational, long-acting HIV-1 capsid inhibitor. Gilead. News release. June 27, 2022. Accessed June 30, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/6/gilead-resubmits-new-drug-application-to-us-food-and-drug-administration-for-lenacapavir-an-investigational-longacting-hiv1-capsid-inhibitor
2. Gilead receives complete response letter from US FDA for investigational lenacapavir due to vial compatibility issues. Gilead. News release. March 1, 2022. Accessed June 30, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/3/gilead-receives-complete-response-letter-from-us-fda-for-investigational-lenacapavir-due-to-vial-compatibility-issues