Pegylated interferon reduces relapses following bepirovirsen treatment in participants with chronic hepatitis B virus infection on nucleos(t)ide analogues: end of study results from the Phase 2b B-Together study

Background In the B-Clear study, bepirovirsen 300 mg for 24 weeks achieved hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA<lower limit of quantification (LLOQ) for 24 weeks of bepirovirsen in 9% of participants on nucleos[t]ide analogues (NA). The B-Together study assessed if sequential bepirovirsen/pegylated interferon (PegIFN) therapy can improve efficacy rates.

Methods Phase 2b, multicentre, randomised, open-label study. Participants on stable NA with HBsAg>100 IU/mL and HBV DNA<90 IU/mL were randomised 1:1 to bepirovirsen 300 mg once-weekly (plus loading dose on Days 4 and 11) for 24 (Arm 1) or 12 (Arm 2) weeks, followed by up to 24 weeks of PegIFN 180 mcg once-weekly, with 24 (Arm 1) or 36 (Arm 2) weeks follow-up. Participants continued NA therapy. Primary endpoint: proportion of participants with HBsAg and HBV DNA<LLOQ for 24 weeks after planned end of sequential treatment, in the absence of newly initiated antiviral therapy. Safety was assessed.

Results 108 participants were enrolled (Arm 1=55; Arm 2=53). Primary endpoint was achieved by 5 (9%) participants in Arm 1 and 8 (15%) in Arm 2; all responders had baseline HBsAg≤3000 IU/mL. Only bepirovirsen responders benefited from PegIFN. Bepirovirsen did not appear to adversely influence the safety profile of subsequent PegIFN.

Conclusions Sequential therapy with bepirovirsen and PegIFN improved off-treatment response versus bepirovirsen alone (B-Clear), which may be driven by prevention of relapse in bepirovirsen responders. No new safety signals were reported.

Funding GSK(209348).

Previously presented AASLD2023 (42723).

Publikationsverlauf

Artikel online veröffentlicht:
23. Januar 2024