The FDA approved GSK's bepirovirsen for adults with chronic hepatitis B on nucleoside therapy, based on phase 3 trials showing 19% functional cure.
The FDA has approved Hibsago (bepirovirsen), GSK’s antisense oligonucleotide, for adults with chronic hepatitis B who are already taking nucleoside analogue therapy.1 The decision follows approval in Japan and extends the drug to a U.S. patient population GSK estimates at about 1.7 million people.1
Hibsago offers a fixed-duration option aimed at functional cure, which suppressive therapy rarely achieves.1
“Despite current therapies, many people living with chronic hepatitis B remain on treatment indefinitely and continue to face the risk of serious liver complications. For the first time, with Hibsago, US patients have the potential to achieve functional cure after a six-month treatment course, with the added convenience of the option of self-administration after the first dose,” said Tony Wood, chief scientific officer at GSK.1
The indication covers adults without cirrhosis who have received a nucleoside analogue for at least six months, have a suppressed viral load and have surface antigen levels of 3,000 IU/mL or lower, as determined by an FDA-authorized test.1 The agency granted the approval under priority review and Breakthrough Therapy designation.1
Quantitative surface antigen testing determines eligibility, and GSK said several tests are available, including one recently authorized by the agency.1
The approval rests on B-Well 1 and B-Well 2, two replicate, randomized, double-blind, placebo-controlled trials in adults on nucleoside analogue therapy across 29 countries.1,2 Participants received bepirovirsen 300 mg weekly by subcutaneous injection or placebo for 24 weeks.2
In pooled data, 233 of 1,220 treated participants (19%) achieved functional cure, compared with none of 614 on placebo.1 Rates were 20% in B-Well 1 and 19% in B-Well 2 at week 72.2
Among participants with surface antigen at or below 1,000 IU/mL, 200 of 768 (26%) reached functional cure, versus none of 393 on placebo.1 Functional cure means viral DNA and surface antigen remain undetectable for at least 24 weeks after all treatment stops, consistent with guidance from a joint American and European liver disease society conference.1,3
In exploratory analyses, surface antigen fell to 100 IU/mL or lower in 49% of treated participants by week 72.1 GSK described the safety profile as acceptable and consistent with earlier bepirovirsen studies.
The most frequent adverse events were injection-site redness, local pain and a temporary rise in a liver enzyme.1
Chronic hepatitis B affects more than 240 million people worldwide and causes roughly 1.1 million deaths a year, GSK said.1 Nucleoside analogues have been standard of care for decades and produce functional cure in about 1% of patients, according to Pharmaceutical Technology, so many patients remain on treatment indefinitely.1,4
GSK licensed bepirovirsen from Ionis Pharmaceuticals and developed it in collaboration with that company.1 GlobalData, which owns Pharmaceutical Technology, projects sales of $926 million in 2034 in a chronic hepatitis B market it expects to reach $3.2 billion that year.4 Competition is emerging: Gilead Sciences’ selgantolimod is in late-stage trials.4
About four in five treated participants did not meet the functional cure definition, and the trials compared bepirovirsen with placebo rather than with other investigational agents.1,2 The indication excludes patients with cirrhosis and those with surface antigen above 3,000 IU/mL, a narrower group than the full chronic hepatitis B population.
GSK said participants at or below 1,000 IU/mL represent about 45% of diagnosed cases globally.1 The B-Well primary endpoint was functional cure.
For links between low surface antigen and improved patient outcomes, GSK pointed to published literature rather than these trials.1 Whether cure translates into fewer liver complications will require longer follow-up.
GSK said it is advancing regulatory submissions in multiple geographies, with key decisions expected in the coming months.1
