FDA Sets PDUFA Date for Lenacapavir For HIV Prevention
The Prescription Drug User Fee Act (PDUFA) date is set for June 19. And if it is approved, it would be the first and only twice-yearly HIV pre-exposure prophylaxis (PrEP).
Image credit: FDA
This morning, Gilead announced the FDA has accepted its new drug application (NDA) submissions for lenacapavir for the prevention of HIV as PrEP.1
The FDA will review the applications under priority review and has assigned a PDUFA target action date of June 19, 2025. If lenacapavir does get approved, it will be the first and only twice-yearly PrEP.1
Purpose Trials
The NDAs are based on data from the phase 3 PURPOSE 1 and PURPOSE 2 trials conducted by Gilead. In PURPOSE 1, data showed twice-yearly lenacapavir demonstrated zero infections in the lenacapavir group and 100% risk reduction and superiority compared to background HIV incidence (bHIV) for the investigational use of HIV prevention in cisgender women. In PURPOSE 2, there were two HIV infections in the lenacapavir group, demonstrating 99.9% of participants in the lenacapavir group did not acquire HIV infection, a 96% risk reduction in HIV infections, and superiority compared to bHIV among a broad and geographically diverse range of cisgender men and gender-diverse people.1
Read more: Twice-Yearly Lenacapavir May Change the World— If We Make It Work
Lenacapavir Access
At last year’s IAS HIV conference, a poster presented by Fortunak et al offered some analysis looking at utilizing lenacapavir more widely for HIV prevention, despite it not being approved for this indication. After much discussion around access, Gilead is moving forward with an access strategy that prioritizes speed and enables the most efficient paths for the regulatory review, approval of and access to lenacapavir for PrEP in regions around the world.
Earlier this year, Gilead submitted a European Commission marketing authorization application (MAA) and an EU-Medicines for All (EU-M4all) application to the European Medicines Agency (EMA) for lenacapavir for PrEP. The EU-M4all application aims to help facilitate availability of lenacapavir for PrEP in low- and lower-middle-income countries. Through the EU-M4all procedure, national regulatory authorities in these regions can leverage the EU opinion to expedite their review processes, potentially accelerating access to lenacapavir for PrEP.
Multidrug-Resistant Therapy
Lenacapavir was initially developed as therapy for adult patients living with HIV whose infections could not be successfully treated with other available treatments because of resistance, intolerance, or safety considerations. Multidrug resistance is an ongoing clinical management challenge, and in this space, there are limited options.
In March of 2022, Gilead received a CRL from the FDA. The letter cited Chemistry Manufacturing and Controls (CMC) issues relating to the compatibility of lenacapavir with the proposed container vial as the reason for their action. The CRL was not reflective of the therapy itself.
“Gilead intends to provide [the] FDA with a comprehensive plan and corresponding data to use a different vial type. We look forward to discussing this further with [the] 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,” Gilead Chief Medical Officer Merdad Parsey, MD, PhD, said in a statement at the time.2
Gilead worked with the FDA to provide the federal agency with the information and compliance that was needed, and when it was FDA-approved in December 2022, it was a welcome addition for patients and clinicians.
“Today’s approval ushers in a new class of antiretroviral drugs that may help patients with HIV who have run out of treatment options,” Debra Birnkrant, MD, director of the Division of Antivirals in the FDA’s Center for Drug Evaluation and Research, said in a statement when it was approved.2
Lenacapavir is the first of a new class of therapies called capsid inhibitors to be FDA-approved for treating HIV. This antiretroviral works by blocking the HIV-1 virus’ protein shell (the capsid), thereby interfering with multiple essential steps of the viral lifecycle. The approval was based on the data of the CAPELLA study, which was a double-blinded, placebo-controlled global multicenter trial designed to evaluate lenacapavir when administered every 6 months as a subcutaneous injection in heavily treatment-experienced (HTE) people with multidrug-resistant HIV infection.2
The use of lenacapavir for the prevention of HIV is investigational and is not approved anywhere globally. The safety and efficacy of this use has not been established by the FDA. Additionally, Gilead recently submitted applications for lenacapavir for PrEP to the European Medicines Agency.1
