# 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 treatment 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 approved by the US Food and Drug Administration (FDA) 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.
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.
The US Food and Drug Administration granted the application for lenacapavir priority review, fast track, and breakthrough therapy designations.
In 2024, Science named lenacapavir "2024 Breakthrough of the Year", citing its "astonishing 100% efficacy" in one large efficacy trial in women and "99.9% efficacy in gender diverse people who have sex with men," while highlighting that research providing a "new understanding of the structure and function of HIV’s capsid protein" led to the drug's "off-the-charts success".

## Society and culture
### Legal status

In 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.
On 18 February 2025, the FDA accepted Gilead's drug application for twice-yearly lenacapavir under priority review. The target action date was assigned as 19 June 2025.

### Economics

As of 2024 the drug, produced by Gilead, costs US$42,250 for the first year. A study presented in July 2024 found that mass production of a generic version would allow a profit margin of 30% on an annual price of $40 if used by 10 million people. The authors said that lowering world HIV levels significantly would probably require 60 million people to take the drug preventatively.

## Research

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.
Studies have been conducted for the use of lenacapavir in treatment-naive individuals. For virally suppressed individuals switching treatment, early studies have tested lenacapavir injections in combination with infusions of the broadly neutralizing antibodies teropavimab and zinlirvimab as well as lenacapavir with islatravir.
A phase III clinical trial study examined efficacy for pre-exposure HIV prevention (PrEP). It found an incidence rate ratio of 0.00 (as no cases occurred in the lenacapavir group) with a 95% confidence interval of 0.00-0.04 with p<.001. Injection site reactions led to discontinuation by 0.2% of lenacapavir patients
Another lenacapavir phase III study, examined the incidence compared to the background rate for men persons. It found an incidence rate ratio of 0.04 with a 95% confidence interval of 0.01 to 0.18, at p<.001. Injection site reactions led to discontinuation by 1.2% of patients.
Lenacapavir has been found to be effective as HIV pre-exposure prophylaxis (PrEP) in heterosexual cisgender women in Africa. Further studies are ongoing assessing effectiveness in men who have sex with men and people who inject drugs.