A-LB-IAS2021-02605Efficacy and safety of long-acting subcutaneous lenacapavir in phase 2/3 in heavily treatment-experienced people with HIV: week 26 results (Capella study)


J.-M. Molina * (1), S. Segal-Maurer (2), H.-J. Stellbrink (3), A. Castagna (4), M. Berhe (5), G.J. Richmond (6), P.J. Ruane (7), G.I. Sinclair (8), K. Siripassorn (9), H. Wang (10), H. Patel (10), N. Margot (10), H. Dvory-Sobol (10), R.H. Hyland (10), M.S. Rhee (10), J. Baeten (10), E. DeJesus (11) - (1) Hopital Saint Louis, Paris, France, (2) New York Presbyterian Queens, New York, United States, (3) ICH Study Center, Hamburg, Germany, (4) IRCCS Ospedale San Raffaele, Milan, Italy, (5) North Texas Infectious Diseases Consultants, Dallas, United States, (6) Gary J Richmond, MD, PA, Fort Lauderdale, United States, (7) Ruane Clinical Research Group, Los Angeles, United States, (8) PrismHealth North Texas, Dallas, United States, (9) Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, (10) Gilead Sciences Inc., Foster City, United States, (11) Orlando Immunology Center, Orlando, United States


BACKGROUND: Lenacapavir (LEN), a long-acting first-in-class HIV capsid inhibitor with full activity against multidrug-resistant mutants, is in clinical development. The ongoing Phase 2/3 Capella study in heavily treatment-experienced (HTE) people with HIV (PWH) failing their current regimen with multidrug-resistance achieved the primary endpoint demonstrating short term potent antiviral activity of LEN vs placebo during the 14-day functional monotherapy period.
METHODS: In the randomized cohort, participants were randomized (2:1) to add oral LEN or placebo to their failing regimen (600 mg on Day 1[D] and 2 and 300 mg on D8). At D15, those on oral LEN received subcutaneous (SC) LEN 927 mg (Q6M); those on placebo started the oral lead-in, followed by SC Q6M. All randomized participants initiated an investigator-selected, optimized background regimen (OBR) at D15. In the non-randomized cohort, participants started OBR concurrent with LEN (oral lead-in à SC). We report the secondary endpoint of Week 26 (W26) efficacy in the randomized cohort, and additional available efficacy and safety from both cohorts.
RESULTS: 72 participants enrolled: 36 in each cohort. Overall, 25% were female; 38% Black. Median age was 52 years; median CD4 count was 150 cells/µL; mean HIV-1 RNA (VL) was 4.17 log10 c/mL. Resistance to '¥ 2 ARVs in each class was 99%(NRTIs), 97%(NNRTIs), 81%(PIs) and 69%(INSTIs). At W26 in the randomized cohort, 81%(29/36) had VL<50 c/mL via FDA-Snapshot algorithm. In participants with data through W26 from both cohorts, 79%(33/42) had VL<50 c/mL via missing=failure. Median CD4 count increased by 82 cells/µL. Four randomized participants had emergent LEN resistance; 3 suppressed afterwards, one with OBR change and two without. Resistance analysis in non-randomized participants is ongoing. There were no study drug-related serious adverse events (AEs) or AEs leading to discontinuations. LEN-related ISRs occurred in 56% (40/72) and were mostly mild or moderate (38/40). Most common ISRs (>20%) were swelling (26%) and erythema (24%); both resolved within days.
CONCLUSIONS: Subcutaneous LEN in combination with OBR led to sustained virologic suppression in 81% of HTE PWH at W26. LEN was safe and well tolerated. These results support the ongoing evaluation of LEN for treatment and prevention of HIV-1 infection.