Bepirovirsen

Buti M, et al. Journal of Hepatology, 2024.

Bepirovirsen demonstrates promising potential in managing chronic hepatitis B (CHB) when combined sequentially with pegylated interferon-α-2a (Peg-IFN). This innovative approach, explored in the phase IIb B-Together trial, aims to extend the therapeutic response and minimize relapse rates observed with bepirovirsen monotherapy.
In the study, 108 participants on nucleos(t)ide analogue (NA) therapy were randomized to receive bepirovirsen (300 mg weekly) for 24 weeks (Arm 1) or 12 weeks (Arm 2), followed by Peg-IFN (180 μg weekly) for 24 weeks. The primary endpoint-achieving hepatitis B surface antigen (HBsAg) <0.05 IU/mL and HBV DNA Sequential Peg-IFN treatment appeared to reduce post-treatment relapse compared to bepirovirsen alone, as evidenced by indirect comparisons with the B-Clear trial. Importantly, the combination therapy maintained a tolerable safety profile, with treatment-related adverse events being comparable between the two study arms.
This trial underscores the viability of combining antisense oligonucleotide-mediated RNA silencing with immunomodulation to enhance treatment outcomes. Sequential bepirovirsen and Peg-IFN therapy addresses a key limitation of bepirovirsen monotherapy by decreasing relapse rates, particularly in patients with lower baseline HBsAg levels.