Investigational antisense oligonucleotide for chronic HBV infection shows positive results
Treatment with the antisense oligonucleotide bepirovirsen appears to lead to sustained loss of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA in up to 10 percent of patients with chronic HBV infection, according to the results of the phase IIb study B-Clear.
B-Clear included patients with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. They were randomized to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Patients in groups 1, 2, and 3 received loading doses of bepirovirsen.
The composite primary endpoint was an HBsAg level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the scheduled end of bepirovirsen treatment, without newly initiated antiviral medication.
A total of 457 patients, of whom 227 were receiving NA therapy and 230 were not receiving NA therapy, were included in the intention-to-treat analysis. Among those receiving NA therapy, six patients in group 1, six patients in group 2, two patients in group three, and none in group 4 achieved the composite primary endpoint event.
Meanwhile, in the cohort of patients not receiving NA therapy, the composite primary endpoint event occurred in seven patients in group 1, four patients in group two, one patient in group 3, and none in group 4.
Over 12 weeks of treatment, adverse events such as injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels occurred more frequently among bepirovirsen-treated patients (groups 1, 2, and 3) than those who received placebo (group 4).
Bepirovirsen targets all HBV messenger RNAs and acts to reduce the levels of viral proteins. Larger and longer trials are needed to establish the efficacy and safety of bepirovirsen for chronic HBV.