Tenofovir Alafenamide Fumarate

Gilead Sciences’ twice-yearly injectable pre-exposure prophylaxis (PrEP) drug has been approved by the US Food and Drug Administration (FDA) to prevent human immunodeficiency virus (HIV). Yeztugo (lenacapavir), which has been authorised to reduce the risk of sexually-acquired HIV in adults and adolescents weighing at least 35kg, is now the first PrEP option in the US that offers six months of protection against the virus. More than 100 people in the US were diagnosed with HIV every day in 2023. PrEP is highly effective for preventing HIV when taken as prescribed. However, there are barriers surrounding adherence to daily oral therapies, including stigma and low awareness of current options. Among the clinical evidence supporting the FDA’s decision on Yeztugo were results from the late-stage PURPOSE 1 trial, which randomised over 5,300 women and adolescent girls aged 16 to 26 years across sites in South Africa and Uganda to receive Yeztugo or one of Gilead’s once-daily oral PrEP drugs, Descovy (emtricitabine/tenofovir alafenamide) and Truvada (emtricitabine/tenofovir disoproxil fumarate). There were zero HIV infections among the 2,134 participants in the Yeztugo group, 16 among 1,068 in the Truvada group and 39 among 2,136 in the Descovy cohort. Positive results from the phase 3 PURPOSE 2 study, in which Gilead’s drug delivered near-complete (99.9%) protection against HIV infection in a “broad and geographically diverse” range of cisgender men and gender-diverse people, also informed the approval. There were two HIV infections among 2,179 participants in the twice-yearly subcutaneous Yeztugo group. In both trials, Yeztugo also demonstrated superiority of prevention of HIV infections when compared with background HIV incidence and was generally well-tolerated, with no significant or new safety concerns observed. Gilead’s chief executive officer, Daniel O’Day, said: “This is a historic day in the decades-long fight against HIV. Yeztugo is one of the most important scientific breakthroughs of our time and offers a very real opportunity to help end the HIV epidemic. “This is a medicine that only needs to be given twice a year and has shown remarkable outcomes in clinical studies, which means it could transform HIV prevention.”

The FDA has approved Gilead Sciences' long-acting HIV-1 capsid inhibitor Yeztugo (lenacapavir) as the first pre-exposure prophylaxis (PrEP) treatment that can be dosed just twice a year, scoring a major win for the drugmaker's HIV portfolio.Touted by CEO Daniel O'Day as a "historic day" in the decades-long effort to end HIV, Wednesday's approval expands the use of lenacapavir – previously cleared in 2022 under the name Sunlenca for multi-drug-resistant HIV – to include PrEP in adults and adolescents weighing at least 35 kg."Gilead scientists have made it their life's work to end HIV and now, with the FDA approval of Yeztugo and in collaboration with our many partners, we can help to make that goal a reality," O'Day said.Near-complete protectionThe priority review filing was supported by data from two large Phase III trials, where Yeztugo offered near-complete protection: no HIV infections were reported in the PURPOSE 1 study, and just two occurred in the PURPOSE 2 trial. Both showed the injectable drug outperformed daily oral Truvada (emtricitabine/tenofovir disoproxil fumarate) in preventing sexually acquired HIV.Yeztugo carries a boxed warning noting that drug-resistant HIV-1 variants have been observed in people with undiagnosed HIV-1 infection.Betting on preventionFacing pressure from pricing reforms and a lagging oncology pipeline, Gilead has high hopes that Yeztugo can help reinvigorate growth – aiming to help double the size of the PrEP market by the mid-2030s.The company's HIV franchise remains a key revenue driver, generating $4.6 billion in the first quarter, up 6% from the prior year, with flagship therapy Biktarvy accounting for $3.1 billion. Still, Gilead expects HIV sales to remain flat through 2025 before rebounding in 2026. For more, see – Spotlight On: Gilead continues to walk a fine line with lenacapavir.While Yeztugo's list price hasn't yet been announced, Gilead says it is putting in place a broad access strategy through insurer partnerships and offering co-pay assistance programmes that could reduce patient costs to zero for commercially insured individuals. Its medication assistance programme will also provide the treatment free of charge to eligible uninsured patients.Focus on launch"Today's new…PrEP approval is a nice de-risking event," Jefferies analysts wrote. "While not a controversial approval, we now look to execution, and the focus is now on the launch and if they can execute, especially on reimbursement."The analysts expect Gilead to price Yeztugo similarly to its oral PrEP counterpart Descovy (emtricitabine/tenofovir alafenamide), which carries a gross annual cost of about $26,000, though they said the net price may be closer to $20,000 due to more limited use of rebates.Meanwhile, international regulatory filings are underway across multiple markets, with applications submitted to the European Medicines Agency under an accelerated review timeline. Gilead has also filed for approval in Australia, Brazil, Canada, and South Africa, with additional submissions planned for countries including Argentina, Mexico, and Peru following the FDA approval.Gilead has said it was forging ahead with Phase III testing next half of a once-yearly formulation of lenacapavir.