The U.S. Food and Drug Administration (FDA) has approved lenacapavir (Yeztugo) as the first and only injectable pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) administered every 6 months.
The approval applies to adults and adolescents weighing at least 35 kg who are at risk of acquiring HIV through sexual contact.
Lenacapavir is a capsid inhibitor delivered via subcutaneous injection every 26 weeks. It targets multiple stages of the HIV lifecycle. Approval was based on data from two phase III trials—PURPOSE 1 and PURPOSE 2—demonstrating its high efficacy in preventing HIV infection.
In PURPOSE 1, 2,134 cisgender women in sub-Saharan Africa received lenacapavir, with no subsequent HIV infections reported. In PURPOSE 2, which included 2,179 cisgender men and gender-diverse individuals across multiple countries, only two HIV infections occurred, resulting in a 99.9% infection-free rate. In both studies, lenacapavir showed statistical superiority over daily oral Truvada (emtricitabine and tenofovir disoproxil fumarate) and background HIV incidence.
The FDA granted Priority Review and Breakthrough Therapy Designation to lenacapavir, recognizing its potential to improve HIV prevention outcomes.
The most common side effects in individuals receiving lenacapavir were injection site reactions, headache, and nausea. No new safety concerns were reported. However, lenacapavir carries a boxed warning about the risk of drug resistance if used in individuals with undiagnosed HIV; a negative HIV-1 test is required before each injection.
Due to its long-acting profile, lenacapavir can remain in the body for up to 12 months after the last dose. Strict adherence to the dosing schedule is essential. If a scheduled injection is delayed by more than 2 weeks, oral tablets may be used temporarily, with injections resuming within 7 days of the last oral dose.
According to the Centers for Disease Control and Prevention, only about one-third of eligible individuals in the United States are currently prescribed PrEP therapies. Factors such as stigma, daily adherence challenges, and low awareness contribute to low uptake. A twice-yearly regimen may help address these barriers and increase PrEP access in underserved populations.
Gilead Sciences has launched assistance programs to support access to lenacapavir for both insured and uninsured individuals in the United States. Regulatory reviews are ongoing in Europe, South America, Africa, and other regions.
Lenacapavir is also approved in the United States for the treatment of multidrug-resistant HIV. While there is no cure for HIV or AIDS, lenacapavir provides a new long-acting prevention option.
Physicians are advised to confirm HIV-negative status before initiating or continuing treatment and to adhere to the recommended 6-month injection schedule.
Source: GILEAD
