FDA Approves GSK's Hibsago, First Antisense Drug for Chronic Hepatitis B

The U.S. Food and Drug Administration on October 20 approved GSK's Hibsago (bepirovirsen) injection, given with existing antiviral therapy, to treat chronic hepatitis B virus (HBV) infection in certain adults without cirrhosis, the agency announced. The FDA said Hibsago is the first antisense oligonucleotide it has approved for chronic hepatitis B.

The approval covers adults who have taken HBV antiviral therapy for at least six months, have suppressed levels of the virus in their blood, and have hepatitis B surface antigen (HBsAg) levels of 3,000 IU/mL or less, as determined by an FDA-authorized test. The agency also authorized Roche's Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to help select patients and monitor them during treatment.

How the drug is used

Hibsago targets the genetic instructions the virus uses to copy itself and make viral proteins, reducing the amount of virus and surface antigen in the body, according to the FDA. It is injected under the skin for up to 24 weeks alongside the patient's existing hepatitis B medicine, which is continued for at least 24 weeks after the last Hibsago dose. Some patients may then be able to stop their existing medicine if they meet certain health and laboratory requirements, the agency said. GSK said patients have the option of self-administration after the first dose.

The B-Well trials

The FDA said Hibsago was studied in two placebo-controlled trials. GSK identified them as B-Well 1 and B-Well 2, global randomized, double-blind Phase III trials conducted in 29 countries in adults already treated with nucleos(t)ide analogue antivirals.

Across the two trials, 24% of patients who received Hibsago met the requirements to stop their existing medicine, compared with none who received placebo, according to the FDA. Twenty-four weeks after stopping all hepatitis B treatment, 19% of Hibsago patients still had the virus under control with no detectable HBsAg in their blood.

GSK calls that outcome functional cure, defined as HBV DNA and HBsAg remaining undetectable for at least 24 weeks after all treatment stops. In the company's pooled data, 233 of 1,220 bepirovirsen patients reached it, versus 0 of 614 on placebo. In a key secondary endpoint among participants with HBsAg of 1,000 IU/mL or less, the rate was 26% (200 of 768) versus 0 of 393, GSK said. Each trial met its primary endpoint, according to the company.

Safety

Hibsago carries a boxed warning for serious liver reactions and for low platelet counts, which can increase the risk of potentially life-threatening bleeding, the FDA said. It also has warnings for worsening kidney function, serious inflammatory reactions such as vasculitis, and serious risks if the injection is not given properly. The most common side effects, excluding laboratory abnormalities, were injection site reactions, fever, fatigue and headache.

"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," said Wendy Carter, acting director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research.

The FDA granted Hibsago Fast Track and Breakthrough Therapy designations as well as Priority Review. GSK licensed bepirovirsen from Ionis Pharmaceuticals and developed it in collaboration with the company. GSK said the drug is now approved in Japan and the United States, and that it is advancing regulatory submissions in other markets, with key decisions expected in the coming months.

GSK said chronic hepatitis B affects about 1.7 million people in the United States.