By IDSE News Staf
The FDA approved lenacapavir (Yeztugo, Gilead Sciences), an injectable HIV-1 capsid inhibitor, to be used as pre-exposure prophylaxis (PrEP) to reduce the risk for sexually acquired HIV in adults and adolescents weighing at least 35 kg, making it the first and only twice-yearly option for Americans who need or want PrEP.
Data show that almost 100% of participants who received lenacapavir in the phase 3 PURPOSE 1 and PURPOSE 2 trials remained HIV-negative. These trials supported the FDA’s approval.
In the PURPOSE 1 trial (ClinicalTrials.gov Identifier: NCT04994509), data at the primary analysis showed twice-yearly subcutaneous lenacapavir demonstrated zero HIV infections among 2,134 participants in the lenacapavir group, 100% reduction in HIV infections and superiority of prevention of HIV infections when compared with once-daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; Truvada, Gilead) in cisgender women in sub-Saharan Africa.
In the PURPOSE 2 trial (NCT04925752), there were two HIV infections among 2,179 participants in the twice-yearly subcutaneous lenacapavir group, demonstrating 99.9% of patients in the lenacapavir group did not acquire HIV infection and superiority of prevention of HIV infections when compared with once-daily oral F/TDF among a broad and geographically diverse range of cisgender men and gender-diverse people. In both trials, lenacapavir also demonstrated superiority in preventing HIV infections when compared with background HIV incidence and was generally well tolerated, with no significant or new safety concerns identified.
In 2022, only about 1 in 3 (36%) people in the United States who were eligible for PrEP were prescribed a form of it. CDC data show that all populations in the United States are not yet using PrEP at rates that could end transmission of the virus at the population level, with particular gaps for women, Black and Hispanic/Latino people, and those in the South. Data also show that barriers including adherence challenges, stigma and low awareness of existing PrEP options—by both healthcare providers and consumers—contribute to this low uptake of PrEP across multiple populations (J Acquir Immune Defic Syndr 2018;77[2]:119-127).
The potential effect of this limited uptake, adherence and access is underscored by the fact that, in 2023, more than 100 people were diagnosed with HIV every day in the United States.
Lenacapavir injection, 463.5 mg/1.5 mL, is indicated for PrEP to reduce the risk for sexually acquired HIV-1 in adults and adolescents (>35kg) who are at risk for HIV acquisition. Individuals must have a negative HIV-1 test prior to initiating lenacapavir for PrEP. The labeling includes a boxed warning for the development of resistance when used among people with undiagnosed HIV infection.
“Yeztugo could be the transformative PrEP option we’ve been waiting for, offering the potential to boost PrEP uptake and persistence and adding a powerful new tool in our mission to end the HIV epidemic,” said Carlos del Rio, MD, a distinguished professor of medicine in the Division of Infectious Diseases at Emory School of Medicine and co-director of the Emory Center for AIDS Research, in Atlanta. “A twice-yearly injection could greatly address key barriers like adherence and stigma, which individuals on more frequent PrEP dosing regimens, especially daily oral PrEP, can face. We also know that, in research, many people who need or want PrEP preferred less frequent dosing.”
Under the brand name Sunlenca (Gilead), lenacapavir is available in the United states to treat multidrug-resistant HIV with other antiretrovirals.
Gilead is committed to helping to ensure that people without insurance will have access. For those who are eligible, Gilead’s Advancing Access medication assistance program will provide lenacapavir for free. Lenacapavir will be available through Gilead’s Advancing Access Co-Pay Savings Program to reduce out-of-pocket costs.
The FDA granted lenacapavir Priority Review and a Breakthrough Therapy designation.
