FDA approves Hibsago, first antisense treatment for chronic hepatitis B

What the FDA approved

The FDA approved Hibsago, or bepirovirsen, on 20 October for adults with chronic hepatitis B. The agency cleared it as the first antisense oligonucleotide for the infection. GSK developed the drug and licensed it from Ionis.

The label limits treatment to adults without cirrhosis who have taken hepatitis B antiviral therapy for at least six months, have suppressed HBV DNA and have hepatitis B surface antigen, or HBsAg, of 3,000 IU/mL or less. Patients keep taking their usual antiviral during treatment. The FDA also authorized a Roche blood test to measure surface antigen. Several FDA-authorized quantitative surface antigen tests are available, PharmaTimes reported.

Hibsago is injected under the skin for up to 24 weeks. Patients can self-inject after the first dose. They continue their antiviral for at least 24 more weeks after the last injection. Only those who then meet specific lab requirements may try stopping all treatment.

About 1.7 million people in the United States live with chronic hepatitis B, by GSK's estimate. Most take a daily antiviral for years, often for life.

What the trials showed

In pooled phase 3 data from the B-Well 1 and B-Well 2 trials, 233 of 1,220 patients on bepirovirsen, or 19%, still had the virus under control 24 weeks after stopping all hepatitis B treatment. None of the 614 patients on placebo did. The trials enrolled adults already on antiviral therapy in 29 countries.

A functional cure means tests can no longer detect HBV DNA and HBsAg in the blood. It does not mean the virus has left the body. Across both trials, 24% of treated patients met the criteria to stop their usual antiviral, against none on placebo. About four in five treated patients did not reach a functional cure. GSK said standard antivirals achieve a functional cure in less than 1% of patients after a year.

Response tracked with starting antigen levels. Among patients at 1,000 IU/mL or below, 26% reached a functional cure, against 19% across the whole treated group. Bepirovirsen pushed HBsAg to 100 IU/mL or less in 49% of the overall study population. That rate was 62% among those who started at 1,000 IU/mL or below, measured at week 72.

Safety and monitoring

Hibsago carries the FDA's strongest warning for serious liver reactions and low platelet counts. Those counts can raise the risk of life-threatening bleeding. The label says doctors must not use bepirovirsen below a platelet count of 100 x 10^9/L and should check platelets weekly during treatment.

Doctors measure ALT and total bilirubin before treatment and frequently during it. They may interrupt, reduce or stop dosing on the results. Other warnings cover worsening kidney function and serious inflammatory reactions such as vasculitis. The drug is not recommended for patients co-infected with hepatitis D. Common side effects are injection site reactions, fatigue, fever and headache.

Norah Terrault, chief of gastroenterology and hepatology at Keck Medical Center of USC, said liver enzyme flares can occur as HBsAg falls. Patients generally tolerate them well, but they need close follow-up, she said. Patients on stable antiviral therapy are often tested only every six months, she noted.

What comes next

How long a functional cure lasts over many years is not yet known. Whether patients who finish with lower HBsAg but no cure could benefit from a second course is also unknown. Terrault said retreatment has not been studied and longer-term studies are needed to interpret lower antigen levels. She urged clinicians to measure HBsAg periodically in patients on antivirals and to discuss the monitoring burden before starting.

GSK and outside researchers plan to test bepirovirsen in combination with other drugs to see whether effectiveness rises. Cost and insurance coverage are not yet clear.