CATEGORY: IMMUNE HEALTH
Chronic hepatitis B is usually treated with a daily pill that controls the virus but almost never clears it. The prescription has no finish line. Two phase 3 trials have now put one in view. After a six-month course of weekly bepirovirsen injections, about one in five participants reached a functional cure, meaning no detectable virus and no medication at all for at least six months.1 Nobody on placebo got there. And on October 20, the FDA approved the drug, under the brand name Hibsago, as the first treatment of its kind for hepatitis B.
A Drug That Thins the Virus’s Smokescreen
Bepirovirsen is an antisense drug: a short strand of lab-made genetic code that sticks to the virus’s instructions inside liver cells and marks them for destruction. Its main target is the hepatitis B surface antigen, a protein the virus churns out in huge amounts. Researchers believe that flood works like a smokescreen, wearing down the immune system until it stops fighting. Thin the smoke, and the body’s own defenses may find the virus again. The two trials, B-Well 1 and B-Well 2, ran identically across 29 countries and enrolled 1,838 adults who’d been stable on standard antivirals for at least six months and didn’t have cirrhosis, the scarring of advanced liver disease. A randomization list, not anyone’s judgment, sorted each person two to one between weekly shots of the real drug and placebo for 24 weeks, with the usual pills continuing underneath.1
Who Reached Week 72 With Nothing Left to Take
People whose surface antigen disappeared and whose virus stayed suppressed could stop their antiviral pills at week 48. The verdict came at week 72. A functional cure meant the antigen stayed gone and the virus stayed undetectable for at least 24 weeks after every treatment had ended. In B-Well 1, 127 of 650 people on bepirovirsen got there, or 20%. In B-Well 2, it was 106 of 570, or 19%. The placebo count was zero in both. Odds ran highest for people who started with less surface antigen in their blood: 25% to 28% of them were cured, against 5% to 10% of those starting higher. About two thirds of the cured also developed protective antibodies, the same defense a vaccine builds.1 An earlier mid-stage trial of the same drug had pointed the same way, at roughly one in ten.2
Sore Injection Sites and a Closely Watched Liver
The shots weren’t free. During the six treatment months, 89% of people on bepirovirsen reported an adverse event, versus 65% on placebo, with injection-site redness and pain leading the list. The most common severe problem was a temporary surge in liver enzymes, seen in about 6%. It tended to arrive alongside the drop in surface antigen and settled on its own. Three percent quit the drug over side effects. No treatment-related deaths were reported.1 GSK funded, designed and analyzed both trials.
What the Approval Does and Doesn’t Settle
The FDA’s approval covers adults like those studied: no cirrhosis, at least six months on standard antivirals, and surface-antigen levels no higher than 3,000 international units per milliliter. Treatment runs six months, and after the first dose people have the option of giving the weekly shots themselves. Hepatologists have called these the first phase 3 trials to demonstrate a functional cure in this disease. Hundreds of millions of people worldwide live with chronic hepatitis B, and the infection is a leading cause of liver cancer, so even a one-in-five cure rate reaches a lot of lives. What the trials can’t yet show is whether the cures hold for many years, or whether they become fewer cancers and liver failures down the road. Four in five participants didn’t clear the virus. Combination treatments meant to push that rate higher are already being tested.
Key Takeaways
- About one in five adults on bepirovirsen reached a functional cure in two placebo-controlled trials; none did on placebo. Odds were best with lower starting antigen levels.
- Functional cure means the virus is undetectable with no medication. It isn’t eradication, and durability beyond the trials’ 72 weeks isn’t known yet.
- The new approval applies to adults without cirrhosis who are stable on standard antivirals; whether cures translate into fewer liver cancers remains unmeasured.
References
- Hou J, Lim SG, Buti M, et al. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection. New England Journal of Medicine. 2026;394(24):2395–2406. link
- Yuen MF, Lim SG, Plesniak R, et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. New England Journal of Medicine. 2022;387(21):1957–1968. link