Gilead presented new results from the ongoing Phase 2/3 CAPELLA trial evaluating lenacapavir in heavily treatment-experienced people living with multi-drug resistant HIV. The findings demonstrate that lenacapavir, administered subcutaneously every six months in combination with other antiretrovirals, achieved high rates of virologic suppression at Week 26 in people living with HIV whose virus was no longer effectively responding to therapy. Gilead presented this data at the 11th International AIDS Society (IAS) Conference on HIV Science.
CAPELLA, a double-blinded, placebo-controlled global multicenter study, includes men and women living with HIV-1 and is being conducted at research centers in North America, Europe and Asia. The trial enrolled 36 patients with multi-class HIV-1 drug resistance and a detectable viral load while on a failing regimen who were randomly allocated to receive oral lenacapavir or placebo in a 2:1 ratio for 14 days, in addition to continuing their failing regimen (functional monotherapy). An additional 36 participants were enrolled in a separate treatment cohort. Both cohorts are part of the ongoing maintenance period of the study evaluating the safety and efficacy of subcutaneous lenacapavir administered every six months in combination with an optimized background regimen. The primary endpoint was the proportion of patients achieving ≥0.5 log10 copies/mL reduction from baseline in HIV-1 RNA at the end of the functional monotherapy period.
In addition to 81% of patients achieving an undetectable viral load at Week 26, the CAPELLA trial achieved its primary endpoint by demonstrating that a significantly higher proportion of participants randomly allocated to receive lenacapavir (n=24) achieved a clinically meaningful viral load reduction of at least 0.5 log10 copies/mL from baseline compared with those randomly allocated to receive placebo (n=12) during the 14-day functional monotherapy period (88% vs. 17%). Those who received lenacapavir achieved a statistically significantly greater mean decrease in viral load than those who received placebo during the functional monotherapy period (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL).
Gilead has submitted an NDA to the U.S. FDA requesting approval for the treatment of HIV-1 infection in heavily treatment-experienced people with multi-drug resistant HIV-1 infection in combination with other antiretrovirals.
Lenacapavir is a long-acting HIV-1 capsid inhibitor. Lenacapavir’s multi-stage mechanism of action is distinguishable from currently approved classes of antiviral agents and is designed to provide a new avenue for the development of long-acting therapy options for people living with or at risk for HIV-1. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV-1 at multiple stages of its lifecycle and has no known cross resistance to other existing drug classes.