GSK-732461

Gilead is awaiting a readout from a second pivotal trial later this year or early 2025 for a potential FDA filing for lenacapavir as PrEP. (Gilead) For the first time, an HIV PrEP drug candidate has shown zero infections in a phase 3 trial. The result came from the PURPOSE 1 trial evaluating Gilead Sciences’ twice-yearly, subcutaneous lenacapavir in cisgender women and adolescent girls ages 16 to 25 in South Africa and Uganda. Lenacapavir, a capsid inhibitor, is already approved by the FDA under the brand name Sunlenca for use alongside other antiretroviral medications to treat HIV in certain tough cases. The trial enrolled more than 5,300 individuals across 28 sites to receive lenacapavir or either one of Gilead’s daily oral PrEP drugs, Descovy and Truvada. While no infections happened during the trial period among more than 2,000 women in the lenacapavir group, the Descovy group recorded an incidence rate of 2.02 per 100 person-years and the Truvada group 1.69 per 100 person-years. “While we know traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills, as well as potentially help increase PrEP adherence and persistence given its twice-yearly dosing schedule,” Linda-Gail Bekker, Ph.D., director of the Desmond Tutu HIV Center at the University of Cape Town in South Africa and past president of the International AIDS Society, said in a statement. On the trial’s primary endpoint, which pitted lenacapavir against a background incidence rate of 2.41 per 100 person-years, the Gilead drug was found to be significantly better. The drug also achieved superiority against Truvada, a secondary comparator. As such, an independent data monitoring committee has recommended that Gilead stop the blinded phase of the PURPOSE 1 trial at this interim analysis, and that all participants be offered lenacapavir open label. Gilead is conducting multiple trials for lenacapavir under the PURPOSE program. The PURPOSE 2 trial is assessing the long-acting drug for PrEP mainly among cisgender men who have sex with men, transgender men and women in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States. Results from that study are expected in late 2024 or early 2025. Gilead’s plan is to combine the data from both pivotal trials to seek an FDA approval. If approved, the twice-yearly drug could “provide a critical new choice for HIV prevention,” Bekker said. Lenacapavir’s success under a once-every-six-month schedule poses a major threat to GSK’s Apretude, an injection that so far can be administered only up to every two months. While GSK’s HIV-focused subsidiary ViiV Health was first to introduce a long-acting PrEP option, it’s behind Gilead on the ultralong-acting front. GSK plans to launch an every-four-month version of Apretude in 2026 and start a registrational study for a twice-yearly option in 2027, the company said during an investor update in September. By GSK’s estimate, the HIV PrEP market is expected to more than double in size to around 4 billion pounds to 5 billion pounds by 2031, with long-acting injectables taking up about 80% of the market value. “With current data from today (and assuming PURPOSE 2 holds), lenacapavir is probably well situated to garner a significant share” of the PrEP market, William Blair analyst Salim Syed wrote in a Thursday note. Besides efficacy, “compliance improvements (and we’ll see about any price premiums) could also be tailwind to sales,” he added. Wall Street’s consensus estimate has put lenacapavir’s global peak sales at around $3 billion across HIV prevention and treatment, Syed noted. The William Blair analyst suggest the drug could reach $4 billion without adjusting for any development risks.  The success of twice-yearly lenacapavir as PrEP also raises the bar for any future HIV vaccine, which remains elusive after multiple setbacks.  Following Apretude’s FDA approval, GSK has opened up the drug’s intellectual property to the United Nations-backed Medicines Patent Pool, working with generic manufacturers to make the PrEP option for certain poorer countries. Under the framework, licensing deals were signed with Aurobindo, Cipla and Viatris last year. Gilead also recognizes the importance of enabling access to achieve the broadest impact. The company on Thursday said it plans to make a public announcement “regarding its planned access approach for high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries.” Both Gilead and GSK are also working on ultralong-acting regimens for HIV treatment. Gilead looks to provide a phase 2 update later this year for lenacapavir in combination with the company’s broadly neutralizing antibodies. Lenacapavir is also being paired with Merck & Co.’s islatravir as a once-weekly oral candidate.   Editor's Note: The story has been updated with input from a Willaim Blair note.