FDA Approves Hibsago, First Antisense Therapy for Chronic Hepatitis B, for Select Adults

The U.S. Food and Drug Administration on Tuesday approved Hibsago, or bepirovirsen, for a defined group of adults with chronic hepatitis B, giving some patients a chance to eventually come off the long-term antiviral therapy that has long been the standard of care.

The agency said Hibsago, made by GSK plc, is the first FDA-approved antisense oligonucleotide to treat chronic hepatitis B. It is approved for use in combination with existing antiviral therapy in certain adults without cirrhosis who have been taking hepatitis B antivirals for at least six months, have suppressed virus levels in their blood and have hepatitis B surface antigen, or HBsAg, of 3,000 IU/mL or less on an FDA-authorized test.

That matters because current hepatitis B drugs, including nucleos(t)ide analogues such as tenofovir and entecavir, can keep the virus under control for years but rarely lead to loss of HBsAg, a key marker doctors view as the preferred endpoint. In the Phase 3 studies supporting approval, 24% of patients who received Hibsago met the trial requirements to stop their existing antiviral medicine, compared with 0% on placebo. Nineteen percent of Hibsago-treated patients went on to maintain viral control with undetectable HBsAg 24 weeks after stopping all hepatitis B treatment.

In those trials, that outcome amounted to a “functional cure,” meaning sustained loss of HBsAg and hepatitis B viral DNA below the lower limit of quantitation 24 weeks after all therapy ended. The results mark a meaningful step for a disease usually managed with long-term suppression, but they also show the limits of the treatment: most patients in the trials did not reach that endpoint.

Hibsago works differently from standard hepatitis B drugs. It is an antisense oligonucleotide, a type of genetic medicine designed to target HBV RNA, or the virus’ transcripts, to reduce viral proteins including HBsAg. The treatment is given by subcutaneous injection for up to 24 weeks while patients continue their background hepatitis B medicine. After the last Hibsago injection, patients must stay on that background antiviral for at least another 24 weeks. Under the prescribing information, some may later be eligible to stop their existing medicine if they meet monitoring requirements.

The FDA also authorized the Roche Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to help identify appropriate patients and monitor them during treatment. Approval was backed by two global Phase 3 trials, B-Well 1 and B-Well 2, with results published May 28 in the New England Journal of Medicine.

The drug comes with significant safety concerns. Hibsago carries a boxed warning for serious liver reactions and thrombocytopenia, or low platelet counts, which can raise the risk of life-threatening bleeding. The FDA also warned about worsening kidney function, serious inflammatory adverse reactions including vasculitis, and risks tied to improper injection administration. Patients taking the drug will need regular laboratory monitoring.

The most common non-laboratory side effects were injection-site reactions, fever, fatigue and headache.

“For many people living with chronic hepatitis B, treatment can mean taking antiviral medication for years to keep the virus suppressed,” Wendy Carter, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Hibsago provides a new treatment approach that gives some patients the possibility of maintaining control of the virus after all chronic HBV treatment has ended. This approval represents an important advance for people living with this serious disease.”

The disease burden is substantial. The World Health Organization estimates roughly 250 million people worldwide live with chronic hepatitis B. For many of them, treatment has meant years, and often an indefinite period, of viral suppression rather than a finite course with a measurable chance of functional cure. Hibsago does not change that reality for most patients, but for a narrow subgroup it offers a new option with a defined treatment window — and a new set of risks that will require close monitoring.