As reported on FierceBioTech, Gilead Sciences has closed one of its midstage clinical studies evaluating an experimental HIV regimen, following ongoing safety concerns that prompted U.S. regulators to intervene last year.
The company confirmed that it has stopped safety follow-up and formally ended the phase 2/3 Wonders-2 trial after continued discussions with the U.S. Food and Drug Administration. The decision comes nearly a year after the FDA placed a clinical hold on multiple Gilead HIV studies assessing a next-generation oral combination therapy.
Wonders-2, along with the larger Wonders-1 trial, was investigating a weekly oral regimen combining two investigational drugs: GS-1720, an integrase strand transfer inhibitor, and GS-4182, a capsid inhibitor. The studies were designed to compare the new regimen’s ability to suppress HIV viral load against Gilead’s widely used once-daily treatment, Biktarvy. While Wonders-2 enrolled 73 participants, Wonders-1 included approximately 675 people living with HIV.
Both studies were paused in June after some participants receiving the combination therapy experienced decreases in CD4+ T-cell counts along with reductions in overall white blood cell levels. These findings raised safety concerns and triggered the FDA’s clinical hold across the program, which also affected several phase 1 trials testing the compounds individually or together.
According to Gilead, laboratory measures for participants in Wonders-2 have since normalized or returned to baseline levels. Despite this improvement, the regulatory hold remains in effect, and Gilead has chosen not to restart the study.
The company said it is coordinating with investigators to help affected participants transition to standard-of-care HIV treatments. Gilead did not announce changes to the paused Wonders-1 trial, which remains under FDA review.
GS-4182 is a prodrug of lenacapavir, a long-acting capsid inhibitor that has already reshaped parts of the HIV treatment and prevention landscape. Lenacapavir was approved in 2022 for treatment of multidrug-resistant HIV under the brand name Sunlenca and later cleared for twice-yearly use as a preventive agent, marketed as Yeztugo.
Gilead continues to explore long-acting HIV treatment strategies and is developing lenacapavir-based regimens in combination with other investigational integrase inhibitors, including GS-3242, despite the setback in its weekly oral program.
