A randomized phase 2b study of subcutaneous PD-L1 antibody ASC22 in virally suppressed patients with chronic hepatitis B who are HBeAg-negative.

Abstract

Background and aims: Studies have shown that blocking the programmed cell death-1/programmed cell death ligand 1 pathway may lead to a potential cure for HBV infections. ASC22 (envafolimab) is a humanized, single-domain programmed cell death ligand 1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed patients with chronic hepatitis B on nucleos(t)ide analogs.

Approach and results: This randomized, single-blind, phase IIb trial enrolled patients with chronic hepatitis B in 2 cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22, and PBO, respectively. The mean changes in HBsAg from baseline at weeks 24 and 48 were -0.309 ( p < 0.001) and -0.272 ( p < 0.023) log 10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 ( p = 0.007) and -0.205 ( p = 0.12) log 10 IU/mL in the 2.5 mg/kg ASC22 group, and -0.003 and -0.063 log 10 IU/mL in the PBO group, respectively (intent-to-treat population). Three out of 10 patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most adverse events were mild (97.9%). There were no study drug-related serious adverse events in the 1.0 mg/kg ASC22 group.

Conclusions: Subcutaneous administration of 1.0 mg/kg ASC22 once every 2 weeks for 24 weeks was shown to be safe and well-tolerated in virally suppressed patients with chronic hepatitis B on nucleos(t)ide analogs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.