Background:
The broadly neutralizing antibody (bNAb) VH3810109 (N6LS), a CD4-binding site antibody with broad and potent neutralizing activity in vitro, demonstrated robust antiviral effect (median viral load [VL] decline of 1.72 log10 c/mL and maximum viral nadir from baseline [BL] of −2.60 log10 c/mL) when given at 40 mg/kg intravenously (IV) in people with HIV-1 in part 1 of the proof-of-concept BANNER study and a good safety profile in parts 1 and 2. We report efficacy data for N6LS administered IV or subcutaneously (SC) in parts 1 and 2 of BANNER.
Methods:
BANNER is a randomized, open-label, 2-part, multicenter study assessing safety, pharmacokinetics, and antiviral activity of N6LS in treatment-naive adults with VL ≥5000 c/mL. N6LS was evaluated during monotherapy after a single IV infusion or SC injection, followed by 48 weeks of standard-of-care antiretroviral therapy. Monotherapy duration was determined by virologic non-response (VL <0.5 log10 by Day 11) or rebound (VL ≥1.0 log[sub]...[/sub]10 over nadir or <0.5 log[sub]...[/sub]10 from BL).
Results:
Of 62 participants, 8 received 40 mg/kg IV and 6 received 280 mg IV in part 1; 16 received 700 mg IV, 16 received 70 mg IV, and 16 received 700 mg SC in part 2. Most participants were male (94%), White (61%), and Hispanic (82%). Median (range) age was 29 (18-61) years. At BL, median VL ranged from 4.1 to 4.5 log10 c/mL across dose groups. Median (range) maximum VL decline ranged from −0.43 (−1.29 to −0.12; 70 mg IV group) log…10 c/mL to −1.72 (−2.60 to −0.60; 40 mg/kg IV group) log…10 c/mL and was reached in a median of 9 days (Figure). Among responders, median (range) time to rebound ranged from 13 (10-22; 70 mg IV group) days to 35 (12-78; 40 mg/kg IV group) days. Across dose groups, there was a weak-to-moderate correlation between BL viral sensitivity and maximum VL decline. N6LS was well tolerated when given IV or SC, with few drug-related adverse events (AEs) and no serious AEs.
Conclusions:
Robust antiviral activity was observed after IV and SC administration of N6LS; response was correlated with N6LS exposure. Response with SC vs IV dosing was lower and likely due to differences in BL susceptibility, serum antibody levels, and slower time to reach Cmax. Overall, N6LS led to dose-dependent declines in VL consistent with antiviral activity reported for other bNAbs. Results support the ongoing development of N6LS into phase IIb.
