Gilead announced topline results from the Phase 2/3 CAPELLA trial evaluating lenacapavir versus placebo in heavily treatment-experienced patients with multidrug resistant HIV-1 infection. A statistically significant greater proportion of patients receiving lenacapavir met the primary endpoint of a viral load reduction of at least 0.5 log10 copies/mL from baseline compared with those receiving placebo at the end of the 14-day functional monotherapy period. Data from longer-term follow-up of CAPELLA study patients will be presented next year, to be followed by data submission to regulatory authorities for approval.
The CAPELLA trial enrolled 36 adults with multi-class HIV drug resistance and a detectable viral load while on a failing regimen who were randomized 2:1 to receive oral lenacapavir or placebo for 14 days, in addition to continuing their failing regimen (functional monotherapy). Of the 24 people randomized to the lenacapavir group, the median baseline viral load was 4.2 log10 copies/mL and 67% had a CD4 count of less than 200 cells/uL. A statistically significant greater proportion of participants receiving lenacapavir met the primary endpoint of a viral load reduction of at least 0.5 log10 copies/mL from baseline compared with those receiving placebo at the end of the 14-day functional monotherapy period (88% vs. 17%). Additionally, the lenacapavir group achieved a statistically significant greater mean change in viral load versus the placebo group (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL).
Lenacapavir was generally safe and well-tolerated, with no serious adverse events related to study drug observed and no study drug discontinuations for any reason through the 14-day period, including no discontinuations due to adverse events. The most common adverse events observed in this portion of the study include injection site swelling (21%) and injection site nodules (17%), the majority of which were Grade 1 or 2 in severity.
All participants are now being offered open-label lenacapavir added to an optimized background regimen. This ongoing maintenance period of the study is evaluating the subcutaneous administration of lenacapavir every six months as well as the safety and efficacy of lenacapavir in addition to an optimized background regimen at Weeks 26 and 52.
Lenacapavir is being developed as a component of a long-acting regimen in combination with other antiretroviral agents. Lenacapavir disrupts HIV capsid, a multimeric shell that is essential to viral replication, at multiple stages throughout the viral life cycle. Lenacapavir is being evaluated to be administered subcutaneously every six months.
In May 2019, the FDA granted Breakthrough Therapy Designation for lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced patients with multidrug resistance in combination with other antiretroviral drugs.