Conclusions
1 evidence topic · 7 sources
Summary: conclusions for formulary review
- Indication and eligibility: bepirovirsen is indicated in combination with nucleos(t)ide analog reverse transcriptase inhibitor (NrtI) therapy for adults with chronic HBV infection without cirrhosis who “have been on NrtI therapy for at least 6 months and have suppressed HBV deoxyribonucleic acid (DNA)” and have HBsAg levels of 3,000 IU/mL or less by an FDA-authorized test. The FDA authorized the Roche Elecsys HBsAg II quant II RxDx assay as the companion diagnostic. Treatment lasts up to 24 weeks, and NrtI therapy continues for at least 24 weeks after the last injection. The drug is contraindicated in acute hepatic impairment, in cirrhosis with Child-Pugh Class A, B, or C hepatic impairment, and with a platelet count below 100 x 10⁹/L before treatment.
- Phase 3 efficacy: in B-Well 1 and B-Well 2, two randomized, double-blind, placebo-controlled trials in participants receiving stable NrtI therapy, the primary endpoint (sustained HBV DNA suppression and HBsAg not detected 24 weeks after discontinuation of all chronic HBV treatment, assessed at week 72) was met by 127 of 650 bepirovirsen recipients (20%) and 0 of 328 placebo recipients in B-Well 1 (common rate difference 17%; 95% CI, 14.6 to 20.3; p<0.0001), and by 106 of 570 (19%) and 0 of 286 in B-Well 2 (common rate difference 13%; 95% CI, 10.4 to 16.1; p<0.0001). In participants with baseline HBsAg of 1,000 IU/mL or less, the pooled rate was 26% (200 of 768) vs 0 of 393.
- Durability after NrtI cessation: 295 of 1,220 pooled bepirovirsen recipients met the criteria to stop NrtI therapy and stopped it at week 48. Of these, 233 (79%) met the primary endpoint at week 72, and 211 of the 233 (91%) maintained response off all HBV treatment at week 96. Of the 84 participants who stopped NrtI therapy without a sustained response through week 96, one met protocol criteria to restart NrtI therapy and three others restarted it within one month of cessation without meeting those criteria.
- Boxed warning: bepirovirsen may cause on-treatment hepatic flares with ALT increases of more than 20 to 40 times the upper limit of normal, some with hyperbilirubinemia, most in the first 12 weeks; ALT and total bilirubin are measured before and frequently during treatment. It may also cause “sudden and unpredictable thrombocytopenia, which can be life-threatening”; platelet counts are monitored weekly at 75 x 10⁹/L or greater and more often below that value, and treatment is permanently discontinued if the count falls below 50 x 10⁹/L. Two participants had serious thrombocytopenia below 50 × 10⁹/L, one with immune thrombocytopenia.
- Follow-up and comparator: the primary endpoint was measured 24 weeks after NrtI cessation, and the longest reported follow-up off treatment covers the 295 participants monitored for an additional 48 weeks after stopping NrtI therapy at week 48. Both trials randomized participants to bepirovirsen or placebo added to background NrtI therapy and had no active-comparator group.
- Patient-reported outcomes: neither the label nor the published abstract reports health-related quality of life or patient-reported outcome results.
- Price and budget impact: no U.S. wholesale acquisition cost has been published; GSK stated that the “list price will become public once pricing and reimbursement discussions have wrapped with payers”. No U.S. budget impact model or U.S. cost-effectiveness analysis of bepirovirsen has been published.
- Ongoing studies: B-United (283 participants, bepirovirsen after daplusiran/tomligisiran) and B-Focus (153 participants with HIV-1 and HBV coinfection) are active, not recruiting, with estimated primary completion in May 2027 and April 2027, respectively, and no posted results.