The US Food and Drug Administration has approved Hibsago (bepirovirsen), the first antisense oligonucleotide for chronic hepatitis B, offering a finite treatment course that can lead to a functional cure for some patients. The approval, announced on October 20, 2026, marks a shift from the current standard of lifelong viral suppression to a time-limited therapy that allows a portion of patients to stop all antiviral medication.
How Hibsago Differs From Lifelong Antiviral Therapy
For decades, the standard of care for chronic hepatitis B has been nucleos(t)ide analogue (NA) therapy. These oral medications effectively suppress the virus but must typically be taken indefinitely to maintain control. If a patient stops treatment, the virus usually rebounds. Hibsago works differently. It is an antisense oligonucleotide that targets the viral messenger RNA, reducing the production of hepatitis B surface antigen (HBsAg) and new virus particles. It is administered as a weekly subcutaneous injection for 24 weeks, taken alongside a patient’s existing NA therapy. After the Hibsago course ends, patients continue their NA medication for at least another 24 weeks. Those who meet specific laboratory and health criteria may then be eligible to stop all hepatitis B treatment.
Who Qualifies for This Treatment
The FDA indication is specific. Hibsago is approved for adults without cirrhosis who have been on stable NA therapy for at least six months. They must have suppressed HBV DNA levels and a quantitative HBsAg level of 3,000 IU/mL or less, as measured by an FDA-authorized test. The agency also authorized the Roche Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to identify eligible patients and monitor them during treatment. An estimated 1.7 million people in the United States live with chronic HBV, according to GSK, though only a subset will meet these criteria. Health Canada approved the drug for the same non-cirrhotic population on November 3, 2026, under Priority Review, and Japan granted approval in August 2026.
Clinical Trial Results: Functional Cure Rates and Durability
The approval rests on the phase 3 B-Well 1 and B-Well 2 trials, global double-blind studies published in the New England Journal of Medicine. In B-Well 1, 20% of patients (127 of 650) receiving bepirovirsen achieved a functional cure at week 72, defined as sustained undetectable HBV DNA and HBsAg loss for at least 24 weeks after finishing all therapy. No patients in the placebo arms achieved a functional cure. Functional cure rates were higher in patients with baseline HBsAg levels at or below 1,000 IU/mL, reaching 26% in that subgroup in the Canadian trial analysis. Model-based extrapolations presented at The Liver Meeting 2026 suggested rates of 46% to 53% for patients with baseline HBsAg below 100 IU/mL, though these are manufacturer-generated predictions, not direct trial results.
The encouraging part is the durability data. Among patients who achieved functional cure, stopped their NA therapy, and completed follow-up, 90% in B-Well 1 and 92% in B-Well 2 maintained the response at week 96 — 48 weeks after all hepatitis B treatment had ended. One patient who stopped NA therapy experienced a viral relapse and restarted treatment after week 72.
Safety Profile and Boxed Warning
The US prescribing label carries a boxed warning for serious liver reactions and thrombocytopenia (low platelet counts), which can increase the risk of potentially life-threatening bleeding. Additional warnings cover worsening kidney function, vasculitis, and risks related to improper injection administration. In the durability follow-up period (weeks 73 to 96), the most common adverse events were upper respiratory tract infection (4%), decreased creatinine renal clearance (2%), and nasopharyngitis (2%). Treatment-related adverse events in that period occurred in 2% of patients and were single events. Investigators described the safety profile as acceptable without evidence of latent safety concerns from prior bepirovirsen treatment.
A New Clinical Pathway
The approval introduces an eight-step US care pathway developed by a multidisciplinary panel of clinicians, pharmacists, and advocates to guide the transition from chronic viral suppression to finite functional cure therapy. The pathway emphasizes shared decision-making, quantitative HBsAg testing, patient engagement tools, and care coordination. Patients should talk to their doctor to see if they meet the eligibility criteria and to discuss the monitoring required during and after the finite treatment course.
Sources
- FDA Approves First-of-Its-Kind Chronic Hepatitis B Treatment
- Bepirovirsen
- Breakthrough: FDA Approves First Drug Offering a 'Functional Cure' For Chronic Hepatitis B
- Hibsago (bepirovirsen) approved in Canada as the first and only finite therapy indicated to achieve functional cure of chronic hepatitis B
- FDA October 2026: New drug approvals, expanding indications and regulatory change
- Hepatitis B Functional Cure Persists Off Treatment After Bepirovirsen | AJMC
Photo: National Cancer Institute / Unsplash (Unsplash License)
