FDA Approves First Hepatitis B Drug Aimed at a Functional Cure

The US Food and Drug Administration has approved the first drug for chronic hepatitis B that can leave some patients free of all treatment. The drug, bepirovirsen, sold as Hibsago by GSK, won approval on October 20 for adults who are already taking standard antiviral tablets. In the trials behind the decision, 19 percent of patients who received the drug reached what doctors call a functional cure, against none on placebo.

What functional cure means

Chronic hepatitis B is usually managed, not cured. Standard antivirals suppress the virus for as long as patients keep taking them, often for years or for life, and the virus usually returns when treatment stops. A functional cure is different: the virus's DNA and its surface antigen stay undetectable in the blood for at least 24 weeks after every hepatitis B medicine has been stopped. The virus is not wiped out of the body, but the patient's own system keeps it under control without drugs.

Bepirovirsen works in a new way for this disease. It is an antisense oligonucleotide, a short piece of engineered genetic material designed to find the virus's RNA messages and destroy them before they can be turned into proteins. It is given as a weekly injection under the skin for up to 24 weeks, alongside the antiviral tablets patients already take, and patients can give themselves the injections at home after the first dose. It is the first drug of its type approved for hepatitis B. GSK licensed it from Ionis Pharmaceuticals.

The trial numbers

The approval rests on the phase 3 B-Well 1 and B-Well 2 trials. In pooled results, 19 percent of bepirovirsen patients, 233 of 1,220, reached functional cure, compared with 0 of 614 patients on placebo. Twenty-four percent met the criteria to stop their existing antiviral medication. Among patients who started with lower surface antigen levels, at or below 1,000 IU/mL, the functional cure rate was 26 percent.

The label is narrow by design. Eligible patients are adults without cirrhosis who have taken a nucleoside analogue antiviral for at least six months, have a suppressed viral load, and have surface antigen levels of 3,000 IU/mL or lower on an FDA-authorized test. The agency also authorized a Roche test to select patients and monitor treatment. Reported side effects include injection site redness and pain and rises in liver enzymes, and the label carries a boxed warning, so patients on the drug need monitoring.

Reaction and what is next

"For many people living with chronic hepatitis B, treatment can mean taking antiviral medication for years to keep the virus suppressed," said Wendy Carter, acting director of the Office of Infectious Diseases in the FDA's drug evaluation center. "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." GSK's chief scientific officer, Tony Wood, said US patients now have the potential to achieve functional cure after a six-month course for the first time. GSK estimates about 1.7 million people in the United States live with chronic hepatitis B. The drug was approved earlier in Japan, and the FDA decision came under priority review with breakthrough therapy status.