Bepirovirsen in Chronic Hepatitis B Infection – Results from Phase 2B Trial

Bepirovirsen 300mg once a week for 24 weeks resulted in up to 10% sustained clearance of hepatitis B virus (HBV) and hepatitis B surface antigens (HBcAg) among patients with chronic HBV infection, according to the results from the phase 2B trial.

The findings of the study are published in the New England Journal of Medicine.

“Bepirovirsen is an antisense oligonucleotide that targets all HBV messenger RNAs and acts to decrease levels of viral proteins,” the researchers explained. “We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue therapy.”

The participants were randomly divided in groups with group 1 receiving subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks; group 2 receiving bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks; group 3 receiving bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks; and group 4 receiving placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks.

The primary outcome was the HBsAg level at the end of 24 weeks.

Out of the 457 total participants, 227 were receiving nucleotide analogue therapy. Among those receiving the therapy, a primary-outcome event occurred in 9% of the participants in both groups 1 and 2 each, but only 3% in group 3 and 0% in group 4. Among those not receiving nucleotide analogue therapy, a primary-outcome event occurred in 10% of the participants in group 1, but only 6% in group 2, 1% in group 3 and 0% in group 4.

Bepirovirsen was more associated with injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, compared to placebo, the researchers observed.

While bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in “sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection,” the investigators cautioned, “larger and longer trials are required to assess the efficacy and safety of bepirovirsen.”

—Priyam Vora

Reference:
Yuen MF, Lim SG, Plesniak R et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. The New England Journal of Medicine. 2022; 387:1957-1968. DOI: nejm.org/doi/full/10.1056/NEJMoa2210027