China: Bepirovirsen at a dose of 300 mg per week sustained clearance of hepatitis B virus (HBV) DNA and surface antigen (HBsAg) in 9 to 10% of patients with chronic HBV infection, according to findings from a phase 2b trial.
The findings were presented at the annual Liver Meeting by the American Association for the Study of Liver Diseases and simultaneously in the NEJM (New England Journal of Medicine).
Bepirovirsen is an antisense RNA-based therapy that targets all HBV messenger RNAs and acts to reduce levels of viral proteins. Man-Fung Yuen, Queen Mary Hospital, Hong Kong, China, and colleagues conducted a phase 2b, randomized, investigator-unblinded trial comprising patients with chronic hepatitis B virus infection who received or did not receive nucleoside or nucleotide analogue therapy.
The patients were randomly assigned in a ratio of 3:3:3:1 to receive weekly subcutaneous injections of bepirovirsen at 300 mg dose for 24 weeks (group 1), bepirovirsen at 300 mg dose for 12 weeks, then 150 mg for 12 weeks (group 2), bepirovirsen at 300 mg dose for 12 weeks then a placebo for 12 weeks (group 3) or placebo for 12 weeks then bepirovirsen at a 300 mg dose for 12 weeks (group 4). Loading doses of bepirovirsen were given to patients in groups 1, 2, and 3.
The composite primary outcome of the study was a hepatitis B surface antigen below the detection limit and an HBV DNA level below the quantification limit maintained for 24 weeks following the planned end of the bepirovirsen treatment without new initiation of antiviral medications.
The study led to the following findings:
- The intention-to-treat population comprised 457 participants; 227 received NA therapy, and 230 did not receive NA therapy).
- Among those who received NA therapy, a primary-outcome event occurred in 9% of participants in group 1, 9% in group 2, 3% in group 3, and 0% in group 4.
- Among those who did not receive NA therapy, a primary-outcome event occurred in 10%, 6%, 1%, and 0%.
- During weeks 1 through 12, injection-site reactions, fatigue, pyrexia and increased alanine aminotransferase levels (adverse events) were more familiar with bepirovirsen (groups 1, 2, and 3) compared to placebo (group 4).
“Bepirovirsen sustained clearance of both HBV surface antigen and DNA for a modest proportion of patients out to 6 months following stoppage of injections,” the researchers wrote. “Longer and larger trials are needed to examine the safety and efficacy of bepirovirsen.”
At that point, 9% of patients with chronic HBV infection either got two 24-week dose regimens for SC injections of bepirovirsen and nucleoside analogues, and 10% remained below quantification or detection level not taking NA but on the highest dose of bepirovirsen for 24 weeks.
Reference:
The study, “Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection,” was published in the New England Journal of Medicine (NEJM).
DOI: 10.1056/NEJMoa2210027