Clinical Scorecard: FDA approves first antisense therapy for hepatitis B

At a Glance

Key Highlights

• Bepirovirsen (Hibsago) is the first FDA-approved antisense oligonucleotide therapy for chronic HBV infection.
• Approval was supported by the randomized, double-blind, placebo-controlled phase 3 B-Well 1 and B-Well 2 trials.
• Pooled functional cure rates were 19% with bepirovirsen plus antiviral therapy and 0% with placebo plus antiviral therapy.
• Among patients with baseline HBsAg levels of 1,000 IU/mL or less, functional cure occurred in 26% receiving bepirovirsen and 0% receiving placebo.
• Bepirovirsen is given by subcutaneous injection for up to 24 weeks; existing antiviral therapy must continue for at least 24 weeks after the final injection.

Guideline-Based Recommendations

Diagnosis

• Use the FDA-authorized test to confirm HBsAg levels of 3,000 IU/mL or less when identifying eligible patients.
• Roche's Elecsys HBsAg II quant II RxDx assay was authorized as a companion diagnostic to help identify eligible patients and monitor treatment.

Management

• Administer bepirovirsen alongside existing antiviral therapy for up to 24 weeks.
• Continue existing antiviral therapy for at least 24 weeks after the final bepirovirsen injection.
• Discontinue existing antiviral medication only when specified clinical and laboratory stopping criteria are met.

Monitoring & Follow-up

• Use the authorized companion diagnostic to help monitor treatment.
• Assess clinical and laboratory criteria before discontinuing existing antiviral therapy.

Risks

• Boxed warnings include serious liver reactions and low platelet counts, including potentially life-threatening bleeding.
• Additional risks include worsening kidney function, serious inflammatory reactions such as vasculitis, and complications from improper injection.
• Common adverse reactions include injection-site reactions, fever, fatigue, and headache.

Patient & Prescribing Data

Adults with chronic HBV infection without cirrhosis who have received nucleos(t)ide analogue antiviral therapy for at least 6 months, have suppressed HBV DNA, and have HBsAg levels of 3,000 IU/mL or less.

In pooled phase 3 results, 233 of 1,220 patients (19%) receiving bepirovirsen achieved functional cure, defined as sustained HBV DNA suppression and undetectable HBsAg for at least 24 weeks after all treatment stopped, versus 0 of 614 placebo recipients. Twenty-four percent of bepirovirsen-treated patients met criteria to discontinue existing antiviral medication, versus 0% receiving placebo.

Clinical Best Practices

• Confirm eligibility using the specified clinical criteria and an FDA-authorized HBsAg test.
• Maintain existing antiviral therapy during bepirovirsen treatment and for at least 24 weeks after the final injection.
• Apply the specified clinical and laboratory stopping criteria before discontinuing antiviral medication.
• Monitor for the serious reactions and other risks described in the prescribing information.

Related Resources & Content

• FDA
• GSK