Gilead Sciences has chosen a partner for lenacapavir in the race to develop new low-frequency treatments for HIV. After comparing two phase 1 integrase strand transfer inhibitors, the Bay Area pharma has elected to pair GS-3242 with lenacapavir as a twice-yearly injectable treatment candidate moving forward and not GS-1219, Gilead announced during its third-quarter earnings call Oct. 30.
Accordingly, a phase 1 study of GS-1219 in people with HIV has been scrapped.
“Our strategy has been to set up our pipeline for multiple shots on goal and then choose the best option for each dosing frequency,” Dietmar Berger, M.D., Ph.D., Gilead’s chief medical officer, said during the call. “We have now chosen to prioritize the development of GS-3242 over GS-1219, and we expect to share more details on GS-3242 at a virology conference in 2026.”
Gilead laid out this plan during an HIV analyst and investor event (PDF) on Dec. 10, 2024.
Twice-yearly lenacapavir was approved for HIV prevention as Yeztugo in June, which Gilead CEO Daniel O’Day hailed as “one of the most important scientific breakthroughs of our time.” Others agreed, with Science naming lenacapavir its 2024 Breakthrough of the Year after the injectable capsid inhibitor aced a large phase 3 trial with an unprecedented 100% efficacy rate.
But the molecule first found success as a long-acting HIV treatment, with a 2022 approval as Sunlenca for patients whose disease has become resistant to multiple other treatments.
Gilead is now looking to turn lenacapavir into a pipeline gift that keeps on giving. In addition to pairing the med with GS-3242 for twice-yearly injectable treatment, the pharma is also teaming lenacapavir with Merck’s islatravir in a phase 3 trial for weekly oral treatment, and with Gilead’s own bictegravir, another integrase inhibitor that is part of the Biktarvy cocktail, in a phase 3 study for daily oral treatment.
Another phase 1 partner for lenacapavir is GS-1614, a prodrug of islatravir that Gilead is testing as a potential quarterly injectable HIV treatment.
A pair of phase 2/3 trials testing yet another two of Gilead’s investigational HIV treatments, GS-1720 and GS-4182, were put on hold by the FDA in June due to safety concerns, with the holds still in effect, according to Gilead’s Oct. 30 presentation.