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HBV Functional Cure
A Monumental Moment: Advances Toward HBV Functional Cure From EASL 2026

Released: June 11, 2026

Jordan J. Feld
Jordan J. Feld, MD, MPH
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Key Takeaways
  • In phase III clinical trials of the antisense oligonucleotide bepirovirsen, the greatest improvement in functional cure rate was observed among people who started with HBsAg <1000 IU/mL.
  • If approved, healthcare professionals should consider who could be good candidates for this drug and how to structure systems in their clinics to administer injectable therapy with consistent monitoring.

To me, there is no question that the biggest news at EASL 2026 was the presentation of final results from the phase III B-Well 1 and 2 trials for the antisense oligonucleotide bepirovirsen. I think this is a very exciting time for the field.

Although bepirovirsen is the furthest along in the development pipeline, other agents are advancing forward as well. In particular, there is another antisense oligonucleotide, AHB-137, that has been studied in China, with results that appear to be similar to those observed with bepirovirsen. Further studies are needed to confirm these results, but these data seem to confirm the promise of the antisense oligonucleotide approach.

This is a monumental moment. The antisense oligonucleotide is the first potential class for chronic hepatitis B treatment with a new mechanism of action since nucleoside and nucleotide therapy was developed in the 1990s. These results are the culmination of many years of research, so finally seeing these clinical trials come to fruition is quite exciting. I think this is the beginning of a new era for chronic hepatitis B management.

Phase III Study Final Results
The final results of the B-Well bepirovirsen studies demonstrated that, when added to nucleos(t)ide therapy, it achieved the primary endpoint of significantly increasing functional cure rates compared with placebo at Week 72.

To understand which patients would be most likely to benefit from bepirovirsen, we should begin by considering the B-Well study participants. The study enrolled people who were on stable nucleos(t)ide therapy, did not have cirrhosis, and had a quantitative hepatitis B surface antigen (HBsAg) level of 100-3000 IU/mL. Participants could be hepatitis B e antigen negative or positive, but most were negative.

If participants were HBsAg negative and had undetectable HBV DNA after treatment, they were able to come off therapy. Participants then were followed for another 6 months to see if they achieved functional cure, defined as remaining HBsAg negative with undetectable HBV DNA. The results showed that approximately 20% of people met that functional cure endpoint.

It is interesting to break those results down to see if the people who achieved functional cure had anything in common. There were no obvious differences in functional cure rates between different sexes, ethnicities, or viral genotypes, but those things may come out as more careful analysis is done.

However, if we look only at the people who started with HBsAg <1000 IU/mL, the functional cure rate increases to approximately 25% to 28%, whereas among people who started with HBsAg 1000-3000 IU/mL, the functional cure rate decreases to approximately 5% to 10% . This distinction clearly shows that the lower the HBsAg level, the better people respond to this treatment.

As a more thorough analysis is done, I believe investigators may be able to identify people who are even more likely to respond, hopefully increasing the probability of functional cure to 40% to 50% in certain populations.

Considerations for Implementation
What might all this mean in practice?

First, healthcare professionals must be able to measure quantitative HBsAg. Those tests are not used routinely in clinical practice, even though they have been around for a long time. Second, candidates for treatment with bepirovirsen would need to already be on stable nucleos(t)ide therapy. Fortunately, the clinical practice guidelines have moved toward more a permissive approach to treatment, where patients in the “gray” or “indeterminate” zone might be eligible for nucleos(t)ide therapy. The key is that if patients will initiate bepirovirsen, their hepatitis B virus (HBV) must be virologically suppressed on nucleos(t)ide therapy first.

On the clinic side, healthcare professionals should be thinking about how they will structure systems in the clinic to be able to administer injectable therapy and how to make more intensive monitoring with frequent blood work feasible.

Safety
Bepirovirsen was safe and well tolerated overall. The main adverse events associated with this drug were predictable alanine aminotransferase (ALT) flares, which were actually associated with HBsAg loss. In general, people with higher ALT flares had a higher chance of HBsAg clearance, and most people with HBsAg loss experienced an ALT increase.

Most ALT flares were relatively modest, but the observed increases suggest that healthcare professionals should carefully monitor for liver disease progression. The studies excluded people with cirrhosis, but if we start to move this drug into real-world practice, it will be crucial to make sure that people with more advanced liver disease are able to take this drug safely.

Other common adverse events included modest reductions in platelet counts that returned to near baseline by Week 72, and mild injection site reactions, which generally resolved with stopping treatment. Only 2% of serious adverse events were deemed related to the treatment, and few people stopped treatment because of adverse events.

I expect that, with good patient selection and consistent monitoring, bepirovirsen will be safe and effective for most people.

Ultimately, I would look at bepirovirsen as the first step toward making functional cure an achievable goal of HBV therapy. Like the first direct-acting antivirals for hepatitis C, bepirovirsen is a big advance, but it is still an incremental step toward a greater goal.

To learn more about advances like this in HBV treatment, join me and my colleague Su Wang, MD, MPH, FACP, for a live, online webinar where we will discuss insights on the latest developments in functional cure.

Your Thoughts
How do you think these advances will change HBV management in your practice? Leave a comment to join the discussion!

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