Lenacapavir

Lenacapavir, sold under the brand name Sunlenca, is an antiretroviral medication used to treat HIV/AIDS. It is taken by mouth or by subcutaneous injection.

The most common side effects include reactions at the injection site and nausea.

Lenacapavir was approved for medical use in the European Union in August 2022, in Canada in November 2022, and in the United States in December 2022. It is the first of a class of drugs called capsid inhibitors to be FDA-approved for treating HIV/AIDS.

Medical uses
Lenacapavir, in combination with other antiretrovirals, is indicated for the treatment of HIV/AIDS. It is used in heavily treatment-experienced adults with multiple drug resistance in whom current antiretroviral therapy is ineffective due to resistance, intolerance or safety considerations.

Mechanism of action
Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation. The US Food and Drug Administration considers it to be a first-in-class medication.

History
Lenacapavir was developed by Gilead Sciences.

As of 2021, it is in phase II/III clinical trials. It is being investigated as a treatment for HIV patients infected with multidrug-resistant virus and as a twice-yearly injectable for pre-exposure prophylaxis.

The safety and efficacy of lenacapavir were established through a multicenter clinical trial with 72 participants whose HIV infections were resistant to multiple classes of HIV medications. These participants had to have high levels of virus in their blood despite being on antiretroviral drugs. Participants were enrolled into one of two study groups. One group was randomized to receive either lenacapavir or placebo in a double-blind fashion, and the other group received open-label lenacapavir. The primary measure of efficacy was the proportion of participants in the randomized study group who achieved a certain level of reduction in virus during the initial 14 days compared to baseline.

As of 2023, lenacapavir was approved by the FDA and EMA for people with limited treatment options. Studies have also been conducted for its use in treatment-naive individuals. For virally suppressed individuals switching treatment, early studies have tested lenacapavir injections in combination with infusions of the broadly neutralising antibodies teropavimab and zinlirvimab (a twice yearly regimen) as well as lenacapavir with islatravir (a weekly oral regimen).

The U.S. Food and Drug Administration granted the application for lenacapavir priority review, fast track, and breakthrough therapy designations.

Legal status
On 23 June 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Sunlenca, intended for the treatment of adults with multidrug‑resistant human immunodeficiency virus type 1 (HIV‑1) infection. The applicant for this medicinal product is Gilead Sciences Ireland UC.

Lenacapavir was approved for medical use in the European Union in August 2022, in Canada in November 2022, and in the United States in December 2022.