Hibsago (bepirovirsen): FDA approval, pivotal trial and safety
Approved
Type
Oligonucleotide · Solution
FDA-approved use
To treat chronic hepatitis B virus infection in certain adults without cirrhosis, in combination with existing antiviral therapyWording from FDA's list of novel approvals.
FDA review
Priority review
Company
GlaxoSmithKline
Application
NDA 221276
Specialty
Infectious Disease
Boxed warning: On-treatment hepatic flares and thrombocytopenia
At a glance
Hibsago (bepirovirsen) is an antisense oligonucleotide approved for chronic hepatitis B in adults without cirrhosis, added to nucleos(t)ide analog therapy. Eligible patients have been on analog therapy for at least 6 months with suppressed HBV DNA and HBsAg at or below 3,000 IU/mL. In two phase 3 trials, functional cure at week 72 was 20% and 19% with bepirovirsen versus none with placebo. It carries a boxed warning for on-treatment hepatic flares and thrombocytopenia.
What it is and how it works
Bepirovirsen is an antisense oligonucleotide directed against HBV mRNA, and the trials describe it as targeting HBV transcripts. Nucleos(t)ide analogs suppress viral replication but rarely clear HBsAg. Bepirovirsen is given for a fixed course on top of the analog, with the aim of functional cure: sustained HBV DNA below the lower limit of quantification and HBsAg loss after treatment ends.
Phase 3, randomized, double-blind, placebo-controlled, replicate of B-Well 2. Treatment lasted 24 weeks. Eligible patients stopped analog therapy at 48 weeks.
Patients
978 adults with noncirrhotic chronic HBV infection on stable analog therapy, with HBsAg above 100 to 3,000 IU/mL.
Compared with
Placebo, randomized 2:1, with continued analog therapy.
Primary endpoint
Functional cure at week 72.
Result
Functional cure occurred in 127 of 650 patients (20%) with bepirovirsen versus none of 328 with placebo. The difference was significant.
Other results
Not reported in the sources.
Safety in the trial
Pooled with B-Well 2. Adverse events were seen in 91% with bepirovirsen versus 73% with placebo. Serious events occurred in 7% versus 4%. Grade 3 or higher events occurred in 16% versus 3%. ALT increase was the most common grade 3 event with bepirovirsen (6%).
How does Hibsago (bepirovirsen) compare with the alternatives (Entecavir, Tenofovir disoproxil fumarate, Tenofovir alafenamide) for chronic hepatitis B virus infection in certain adults without cirrhosis, in combination with existing antiviral therapy? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
Phase 3, randomized, double-blind, placebo-controlled replicate of B-Well 1. Treatment lasted 24 weeks. Eligible patients stopped analog therapy at 48 weeks.
Patients
856 adults with noncirrhotic chronic HBV infection on stable analog therapy, with HBsAg above 100 to 3,000 IU/mL.
Compared with
Placebo, randomized 2:1, with continued analog therapy.
Primary endpoint
Functional cure at week 72.
Result
Functional cure occurred in 106 of 570 patients (19%) with bepirovirsen versus none of 286 with placebo. The difference was significant.
Other results
Not reported in the sources.
Safety in the trial
Pooled with B-Well 1. The label's pooled safety set had 1,223 patients on bepirovirsen and 611 on placebo. Common reactions were injection site reactions, pyrexia, fatigue, and headache.
The boxed warning covers on-treatment hepatic flares and thrombocytopenia. Flares involved ALT rises above 20 to 40 times the upper limit of normal, some with hyperbilirubinemia. They occurred mostly in the first 12 weeks and resolved with interruption or discontinuation. Thrombocytopenia can be sudden and life-threatening. The drug is contraindicated with a baseline platelet count below 100 x 10^9/L, and platelet and liver tests need close monitoring. Other warnings include worsening renal function, serious inflammatory and immune reactions, a serious reaction with improper administration, HBV exacerbation after stopping antiviral therapy, and a poor fit with HDV coinfection. Common adverse reactions were injection site reactions, pyrexia, fatigue, and headache.
What it competes with
Chronic hepatitis B is usually treated long term with oral nucleos(t)ide analogs that suppress HBV DNA. Pegylated interferon is an alternative finite-duration option for some patients.
EntecavirOral nucleoside analog with a high barrier to resistance. It is a standard long-term suppressive option.
Tenofovir disoproxil fumarateOral nucleotide analog used for long-term viral suppression. Renal and bone effects need monitoring.
Tenofovir alafenamideOral nucleotide analog with a different renal and bone profile than tenofovir disoproxil. Used for long-term suppression.
Pegylated interferon alfaFinite-duration immune-modulating injection. It is often poorly tolerated and suits selected patients.
Bottom line for clinicians
Hibsago is for noncirrhotic adults with long-suppressed HBV DNA and a low HBsAg level who want a finite course aimed at functional cure. Most treated patients did not reach functional cure in the trials. Weigh this against the risks of flares and thrombocytopenia, the monitoring burden, and renal and immune effects.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 27, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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