VH3810109 Efficacy, Safety, Pharmacokinetics, and Incidence of Anti-drug Antibodies in Adults With HIV-1 Naive to Antiretroviral Therapy: BANNER Study Results

Background VH3810109 (N6LS) is a CD4-binding site antibody with broad and potent neutralizing activity in vitro. Here, we present efficacy, safety, and pharmacokinetic results from the phase 2a BANNER study in people with HIV-1. Methods BANNER was a randomized, open-label, 2-part, multicenter study of N6LS in adults naive to antiretroviral therapy (ART) with HIV-1 RNA ≥5000 copies/mL. N6LS was evaluated during monotherapy after a single intravenous (IV) infusion at various doses or subcutaneous (SC) injection, followed by 48 weeks of standard-of-care ART. Antiviral activity, safety, pharmacokinetics, and anti-drug antibodies (ADAs) were evaluated. Results Sixty-two participants completed the monotherapy phase and 58 completed the standard-of-care phase. Most participants were male (94%), Hispanic (82%), and White (61%). Virologic response (reduction in HIV-1 RNA ≥0.5 log10 copies/mL from baseline) was achieved in 8/8 (100%; 40 mg/kg IV), 14/15 (93%; 700 mg IV), 5/6 (83%; 280 mg IV), 7/16 (44%; 70 mg IV), and 8/16 (50%; 700 mg SC) participants. Administered IV or SC, N6LS was well tolerated with few drug-related adverse events (n=13) and no serious adverse events reported during monotherapy. Pharmacokinetic parameters increased proportionally with dose. Incidence of ADAs was dose-dependent and ranged from 6% to 83% in the IV groups; incidence was 19% in the SC group, with no indication that route of administration impacts incidence of ADAs. Conclusions N6LS was efficacious and generally safe, supporting further development of N6LS dosed IV or SC for the treatment of HIV-1 (ClinicalTrials.gov, NCT04871113).