The FDA approved GSK’s Hibsago (bepirovirsen) on Oct. 20 as the first antisense treatment for chronic hepatitis B. In two placebo-controlled trials, 19% of patients on Hibsago had undetectable hepatitis B surface antigen six months after stopping all therapy. No placebo patient did.
Who Can Receive Hibsago
The FDA said in its approval announcement that the label covers adults without cirrhosis who have taken hepatitis B antiviral therapy for at least six months and have suppressed virus levels in the blood. Their hepatitis B surface antigen, known as HBsAg, must measure 3,000 IU/mL or less on an FDA-authorized test. The agency also authorized the Roche Elecsys HBsAg II quant II RxDx assay to select patients and monitor them during treatment.
Patients receive Hibsago as an injection under the skin for up to 24 weeks. They keep taking their existing hepatitis B medicine during treatment and for at least 24 weeks after the last injection. Some patients may then stop the existing medicine if they meet health and laboratory criteria. The drug works by targeting the viral genetic instructions that the virus uses to copy itself and make its proteins, which reduces the virus and HBsAg in the body, the agency said.
The FDA granted the application Fast Track, Breakthrough Therapy and Priority Review designations. Wendy Carter, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said, “This approval represents an important advance for people living with this serious disease.”
What the B-Well Trials Measured
GSK’s announcement describes two global trials, B-Well 1 and B-Well 2, run in 29 countries. Both were randomized, double-blind and placebo-controlled. Participants were adults on nucleos(t)ide analog therapy with baseline HBsAg of 3,000 IU/mL or less. The primary endpoint was functional cure, measured six months after all therapies stopped. Each trial met it.
Pooled results show functional cure in 233 of 1,220 patients on bepirovirsen, or 19%, against 0 of 614 on placebo. The FDA reported the same pattern in its own terms: 24% of Hibsago patients met criteria to stop their existing medicine, while no placebo patients did, and 24 weeks after stopping all hepatitis B treatment, 19% still had the virus under control with undetectable HBsAg. The FDA’s announcement does not give trial sizes. GSK said standard of care alone typically produces functional cure in under 1% of patients after one year.
Two calculations from GSK’s numbers show the trial design. The ratio of 1,220 to 614 is close to two to one, which suggests patients were assigned to the drug at about twice the rate of placebo. The FDA said 24% could stop their medicine, but 19% held control after stopping. If both figures describe the same group of Hibsago patients, a point the FDA does not state, about four in five patients who qualified to stop their antiviral medicine kept control, which is 19 divided by 24.
Results for Patients with Lower Surface Antigen
Results were stronger in patients who began with lower HBsAg. In the subgroup with baseline HBsAg of 1,000 IU/mL or less, GSK reported functional cure in 200 of 768 patients, or 26%, against 0 of 393 on placebo. That subgroup represents about 45% of diagnosed chronic hepatitis B cases worldwide, according to GSK.
The label reaches higher than the subgroup, up to 3,000 IU/mL, so a calculation shows what happened above the 1,000 line. Subtracting the subgroup from the pooled totals leaves 452 patients on bepirovirsen with higher baseline HBsAg and 33 functional cures among them, which is 7.3%. GSK did not publish that figure. The company did report an exploratory measure at week 72: HBsAg fell to 100 IU/mL or lower in 49% of the overall group (598 of 1,220) and 62% of the lower-antigen subgroup (476 of 768).
Dr. Norah Terrault, chief of gastroenterology and hepatology at USC Keck Medical Center, called the approval “the start of a new era” in treating chronic hepatitis B, according to GSK’s announcement. Dr. Chari Cohen, president of the Hepatitis B Foundation, said in the same release that the disease remains a major public health challenge and that screening, diagnosis and treatment have progressed. Tony Wood, GSK’s chief scientific officer, said patients may reach functional cure after a six-month course and can self-administer after the first dose.
Safety Warnings on the Hibsago Label
Hibsago carries a boxed warning for on-treatment hepatic flares and for low platelet counts, which can raise the risk of life-threatening bleeding, the FDA said. GSK’s label summary says the drug is contraindicated in patients with cirrhosis, acute hepatic impairment or platelet counts below 100 x 10 /L. The FDA also lists warnings for worsening kidney function, serious ⁹ inflammatory reactions such as vasculitis and serious risks if the injection is not given properly. GSK names omental infarction as the risk of improper injection technique.
The most common side effects, excluding laboratory abnormalities, were injection site reactions, fever, fatigue and headache. GSK listed the three most frequent adverse events in the trials as injection site redness, local pain and a temporary rise in a liver enzyme. Patients need regular blood tests and follow-up with a health care provider before and during treatment, the FDA said.
How Many Americans Have Chronic Hepatitis B
Estimates of the U.S. patient population differ. The Centers for Disease Control and Prevention says about 640,000 adults in the United States have chronic hepatitis B. GSK’s announcement puts the figure at about 1.7 million people in the country. The CDC page counts adults and does not state a year, and GSK’s release does not state its basis, so the sources do not explain the gap.
GSK also said more than 240 million people worldwide have chronic hepatitis B, with about 1.1 million deaths a year. The CDC said available medicines are not a cure and help only some people. Without treatment, chronic infection can lead to liver damage, cirrhosis, liver cancer and death.
Next Steps for Hibsago
GSK said Hibsago is approved in the United States and Japan, and that regulatory submissions are under review in other regions with decisions expected in the coming months. The company also cited Breakthrough Therapy and Priority Review designations in China and a SENKU designation in Japan. The company’s announcement gives no U.S. price or launch date.
