Hepatitis B has stalked humanity for millennia. It still infects nearly 300 million people worldwide. Current medicines suppress the virus but rarely eliminate it. Patients face decades of daily pills and the lingering threat of cirrhosis or liver cancer.
New data change that picture for some.
In two large phase 3 trials, an experimental antisense oligonucleotide called bepirovirsen, given for 24 weeks on top of standard nucleoside analogues, produced a functional cure in 19% to 20% of participants. Six months after all treatment stopped, these patients showed undetectable levels of both hepatitis B virus DNA and surface antigen. None in the placebo arms achieved that mark. The results, published in the New England Journal of Medicine, mark the strongest evidence yet that a finite therapy can free selected patients from lifelong suppression.
But. Success came with clear boundaries. Only patients already well-controlled on oral antivirals and with relatively low baseline surface antigen levels responded at meaningful rates. Those with higher antigen loads saw far smaller gains. The drug also carried more side effects than placebo. So the advance lands as both breakthrough and reminder of how far the field still must travel.
Bepirovirsen, developed by Ionis Pharmaceuticals and partnered with GSK, works by binding to HBV messenger RNA. It triggers its destruction. That cuts production of viral proteins, most notably the surface antigen that overwhelms and exhausts the immune system. With antigen levels falling, the body’s own defenses can sometimes regain control. Standard nucleoside analogues, by contrast, block replication but leave antigen production largely untouched.
The B-Well 1 and B-Well 2 trials enrolled more than 1,800 adults with non-cirrhotic chronic infection. All were on stable nucleoside therapy with suppressed viral DNA and surface antigen at or below 3,000 IU per milliliter. Participants received 24 weeks of bepirovirsen or placebo, then continued nucleoside analogues for another 24 weeks before stopping everything. The primary endpoint was functional cure at week 72 — 48 weeks after the last dose of study drug — defined as loss of surface antigen plus undetectable DNA.
Numbers tell the story cleanly. In B-Well 1, 20% of bepirovirsen patients hit the endpoint versus 0% on placebo. B-Well 2 showed 19% versus 0%. Rates climbed to 25-28% among those entering with surface antigen below 1,000 IU per milliliter. They dropped to 5-10% for those between 1,000 and 3,000. The pattern held across both studies. Science reported that 233 of 1,220 bepirovirsen recipients achieved functional cure overall, compared with none of 614 on placebo.
One in five. That figure lands far above the 3% or lower rates of surface antigen loss seen after years of nucleoside therapy alone. Yet it also underscores the limits. Four out of five patients still needed to resume or continue treatment. Durability beyond 72 weeks remains unknown. And the trials excluded people with cirrhosis, HIV coinfection, or high antigen levels — groups that represent large shares of the global burden.
Safety data showed higher rates of grade 3 or greater adverse events: 16% with bepirovirsen versus 3% with placebo, according to CIDRAP’s coverage of the NEJM paper. Elevations in liver enzymes, rises in creatinine, and drops in platelets appeared more often in the treatment arm. Most were manageable. Still, clinicians will watch those signals closely if the drug reaches approval.
Regulatory momentum has built quickly. The FDA accepted GSK’s new drug application for priority review in April 2026 and granted breakthrough therapy designation. A decision is expected by October 26. Ionis CEO Brett Monia called the candidate “uniquely positioned to effectively treat CHB” because it reduces replication, suppresses antigen, and stimulates immunity. The submission rested squarely on the B-Well results.
Experts temper excitement with realism. The New England Journal of Medicine editorial accompanying the trials noted that while functional cure rates above 20% represent real progress, broader application will require better predictors of response and likely combination approaches. Patients with high antigen or advanced disease still lack good options.
Other candidates circle the same goal. Chinese developers have reported higher rates in smaller studies. AusperBio’s AHB-137 antisense molecule achieved a 30% functional cure rate in select patients on nucleoside therapy, per company announcements covered in a Labiotech review of the field. Gene-editing efforts, such as Precision BioSciences’ PBGENE-HBV, have cleared early regulatory hurdles in the U.S. None have yet matched bepirovirsen’s phase 3 scale.
The global picture adds urgency. Most of the 300 million carriers live in Asia and Africa with limited access to sophisticated testing or expensive drugs. A one-size-fits-all cure remains distant. Bepirovirsen, even if approved, would likely serve best as a targeted option for those already on treatment with low antigen — a minority in many regions. Cost and distribution challenges loom large.
Still, the data shift the conversation. For the first time, a sizable fraction of patients in rigorous trials stopped all medicine and stayed virus-free six months later. That outcome was zero in the control groups. The difference is stark. And it opens doors to further refinement — perhaps pairing bepirovirsen with immune modulators or newer agents to push response rates higher and broaden eligibility.
Hepatitis B researchers have chased functional cure for years. These results don’t end the chase. They prove the target sits within reach for some. The next trials will test whether combinations can expand that reach. The patients waiting for relief number in the hundreds of millions. Progress, at last, carries measurable weight.
WebProNews is an iEntry Publication