Background
VH3810109 (N6LS) is a broadly neutralizing CD4-binding site antibody being developed for long-acting HIV-1 therapy. N6LS was well tolerated and efficacious in participants with HIV-1 naive to treatment when administered intravenously (IV) or subcutaneously (SC) in the proof-of-concept phase 2a BANNER study. In the phase 1 SPAN study, single-dose N6LS given IV (60 mg/kg) or SC (3000 mg) with recombinant human hyaluronidase PH20 (rHuPH20) showed a good safety profile in adults without HIV. Using the same doses from SPAN, the EMBRACE study evaluated the efficacy, safety, and tolerability of N6LS every 4 months + long-acting intramuscular cabotegravir (CAB LA) monthly for maintenance of HIV-1 suppression.
Methods
EMBRACE is a phase 2b, randomized, open-label, multicenter study (45 sites; US and Puerto Rico) in adults with screening HIV-1 RNA <50 c/mL and phenotypic sensitivity to N6LS (90% inhibitory concentration [IC90] ≤2.0 µg/mL). Participants were randomized 2:2:1 to N6LS 60 mg/kg IV + CAB LA, N6LS 3000 mg + rHuPH20 SC + CAB LA, or to continue their pre-baseline standard-of-care (SOC) regimen. The primary endpoint was plasma HIV-1 RNA ≥50 c/mL at Month 6 (FDA Snapshot algorithm).
Results
Of 125 participants randomized, median (range) age was 53 (22-69) years and 83% were male; 63% identified as White, 28% as Black or African American, and 43% as Hispanic or Latin American. Proportions with plasma HIV-1 RNA ≥50 c/mL at Month 6 were 2/50 (4%) with N6LS 60 mg/kg IV, 3/49 (6%) with N6LS 3000 mg SC + rHuPH20, and 0/26 (0%) with SOC (Table). Through Month 6, confirmed virologic failure (CVF) occurred in 2 participants receiving N6LS 60 mg/kg IV, 2 receiving N6LS 3000 mg SC + rHuPH20, and 0 receiving SOC. Of 3 participants with data available at CVF, 1 had N6LS IC90 >2 µg/mL and none had integrase resistance mutations. N6LS was well tolerated when given IV or SC + rHuPH20, with AEs leading to withdrawal occurring in 3/49 receiving SC + rHuPH20 and no N6LS/CAB-related serious AEs reported. Grade ≥3 N6LS-related infusion site reactions (ISRs) were reported in 0/50 (0%) participants receiving N6LS 60 mg/kg IV and 7/49 (14%) receiving N6LS 3000 mg SC + rHuPH20; mean (SD) duration of all ISRs was 2.0 (0.8) and 6.4 (5.2) days with N6LS dosed IV or SC + rHuPH20, respectively.
Conclusions
N6LS administered IV or SC + rHuPH20 every 4 months in combination with monthly CAB LA maintained viral suppression in most adults who were sensitive to N6LS at baseline, with tolerability favoring IV N6LS.