Chronic hepatitis B has long been a condition of management rather than resolution, a quiet infection held in check by daily or long-term drugs but seldom truly ended. In Denver, at the AASLD Liver Meeting, Man-Fung Yuen presented end-of-study results from the phase 3 B-Well trials, showing that among patients who reached functional cure with the antisense drug bepirovirsen, nine in ten were still cured nearly a year after stopping all treatment. The approval that followed in October gives this durability a practical setting, but the findings also carry a sober caveat: the chance of cure depen
Bepirovirsen Functional Cure Holds in 91% of Responders Through Week 96 in Chronic Hepatitis B
Functional cure held in 91% of responders, 48 weeks after all treatment stopped
Mark
Why does the 91% matter more than the 19%?
Mimi
Because 19% says how many people got to functional cure. The 91% says whether it lasted once all treatment, including the analogs, was off for 48 weeks.
Luke
Worth being precise, though. The 91% is among responders who stopped analogs and completed Week 96: 211 of 232, pooled from 114/127 and 97/105. It isn't 91% of everyone treated.
Mark
And the baseline HBsAg numbers?
Mimi
They're the practical story. Cure was 40% at Week 72 under 200 IU/mL and 4% at 2500 to 3000.
Luke
Those are post hoc pooled analyses, so they describe patterns, not prespecified tests. Still, they fit the approval's 3000 cutoff.
Mark
What about safety after stopping?
Mimi
Five had HBV DNA replication at Week 72 and one relapsed and restarted analogs. Adverse events later were mostly mild, like upper respiratory infection at 4%.
Luke
Ninety-six weeks is the follow-up here. Whether cure lasts beyond that isn't something this data can say.
Mark
So what happens next?
Mimi
Terrault says quantitative HBsAg testing is central to choosing patients, so that testing will shape who gets it.
Le Pouls
- Chronic hepatitis B has been managed for decades but rarely ended, and patients have lived with suppression rather than release.
- Bepirovirsen, sold as Hibsago, became the first antisense oligonucleotide approved for chronic HBV, granted by the FDA on October 20, 2026.
- Only 19% of treated patients reached functional cure by Week 72, and the rate sinks to 4% for those with the highest baseline HBsAg levels.
- Among those who stopped analog therapy and reached Week 96, 91% kept their cure, signaling that the result is holding rather than fading.
- With approval granted for adults with HBsAg of 3000 IU/mL or less, the next question is how quantitative testing will decide who actually gets treated.
Chronic hepatitis B has long been a condition of management rather than resolution, a quiet infection held in check by daily or long-term drugs but seldom truly ended. In Denver, at the AASLD Liver Meeting, Man-Fung Yuen presented end-of-study results from the phase 3 B-Well trials, showing that among patients who reached functional cure with the antisense drug bepirovirsen, nine in ten were still cured nearly a year after stopping all treatment. The approval that followed in October gives this durability a practical setting, but the findings also carry a sober caveat: the chance of cure depends heavily on how much viral surface antigen a patient carries at the start, reminding us that even a promising therapy meets the limits of the biology it is asked to reverse.
At the AASLD Liver Meeting in Denver, Man-Fung Yuen of the University of Hong Kong presented the end-of-study results from the two phase 3 B-Well trials of bepirovirsen, and the number that stood out was durability. Of the patients with chronic hepatitis B who reached functional cure, 91 percent still had it at Week 96, nearly a year after they had stopped all hepatitis B treatment.
The results arrived shortly after the FDA approved bepirovirsen, sold as Hibsago, on October 20, 2026. It is the first antisense oligonucleotide approved for chronic HBV, to be used alongside nucleos(t)ide analogs in adults without cirrhosis whose HBsAg is 3000 IU/mL or lower.
The trials enrolled patients whose infection was already suppressed by analogs. They received weekly bepirovirsen or placebo for 24 weeks, and eligible participants then stopped their analogs at Week 48. By Week 72, 19 percent of treated patients had reached functional cure, compared with none on placebo, and that figure rose to 26 percent among those with lower baseline antigen levels.
The finding that most shapes who benefits is how strongly baseline HBsAg governed the odds. Cure rates ranged from around 40 percent for patients under 200 IU/mL to just 4 percent for those between 2500 and 3000 IU/mL. Quantitative HBsAg testing, in other words, is central to deciding who may be a good candidate.
With approval now in hand, the open question is how that testing will shape real-world eligibility and uptake.
At the AASLD Liver Meeting in Denver, Man-Fung Yuen of the University of Hong Kong presented end-of-study results from the two phase 3 B-Well trials of bepirovirsen, and the headline number was durability: of patients with chronic hepatitis B who reached functional cure, 91% still had it at Week 96, which is 48 weeks after they stopped all hepatitis B treatment.
The data arrive shortly after regulators acted. On October 20, 2026, the FDA approved bepirovirsen, sold as Hibsago, as the first antisense oligonucleotide for chronic HBV infection. It is approved for use alongside nucleos(t)ide analog therapy in adults without cirrhosis whose hepatitis B surface antigen, or HBsAg, is 3000 IU/mL or lower.
B-Well 1 and B-Well 2 enrolled noncirrhotic adults whose infection was suppressed by nucleos(t)ide analogs, with HBV DNA under 90 IU/mL and HBsAg between 100 and 3000 IU/mL. Participants received either 300 mg of bepirovirsen or placebo weekly for 24 weeks. Those eligible stopped their analog therapy at Week 48. Functional cure meant HBV DNA below the lower limit of quantification and HBsAg loss, sustained for at least 24 weeks off all therapy.
At Week 72, 19% of bepirovirsen recipients (233 of 1220) had reached functional cure, against none of 614 placebo recipients. Among those whose baseline HBsAg was 1000 IU/mL or lower, the rate was 26% (200 of 768), versus 0 of 393 on placebo. After Week 72, 291 bepirovirsen-treated participants who had stopped analogs moved into the durability stage.
Among responders who stopped analogs and completed Week 96, durable functional cure held in 90% (114 of 127) in B-Well 1 and 92% (97 of 105) in B-Well 2, a pooled 91%. Durability was similar in the subgroup with baseline HBsAg of 1000 IU/mL or lower. HBV DNA suppression off all treatment persisted through Week 96 in 96% of participants who had DNA below the quantification limit at Week 72.
Baseline HBsAg strongly shaped the odds. In a post hoc pooled analysis, functional cure rates at Weeks 72 and 96 were 40% and 35% for those under 200 IU/mL, 31% and 30% for 200 to under 300, and 16% and 15% for 500 to under 1000. For those at 2500 to 3000 IU/mL, the rate was 4% at both timepoints.
A broader measure looked better. At Week 72, 49% of bepirovirsen recipients had either achieved functional cure or had quantitative HBsAg of 100 IU/mL or less. In a post hoc analysis of participants with Week 96 data, 97% had HBsAg at or below 100 IU/mL.
On safety after stopping analogs, five participants had HBV DNA replication at Week 72, and one had a viral relapse and restarted analog therapy. From Weeks 73 to 96, the most common adverse events were upper respiratory tract infection (4%; 12 of 291), decreased creatinine renal clearance (2%; 5 of 291) and nasopharyngitis (2%; 5 of 291). Treatment-related adverse events after stopping bepirovirsen occurred in 2% (5 of 291), each a single event.
Norah Terrault, a B-Well coauthor, told HCPLive in a recent interview that quantitative HBsAg testing is central to deciding who may be a candidate. With approval now in place, the thing to watch is how that testing shapes real-world eligibility and uptake.
Citations marquantes
Quantitative HBsAg testing is central to selecting patients who may be candidates for bepirovirsen.— Norah Terrault, MD, MPH, B-Well coauthor (paraphrased)
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