Why This Matters
Chronic hepatitis B infects an estimated 250 to 300 million people worldwide, including approximately 1.9 million Americans. For most of those people, treatment means a lifelong commitment to antiviral medication that suppresses the virus but rarely eliminates it. Stop the drug, and the virus rebounds. The disease persists, and over decades, it silently causes cirrhosis and liver cancer in a significant proportion of patients.
A functional cure changes that equation. It means the immune system has taken over control of the virus, with no detectable viral DNA and no detectable hepatitis B surface antigen sustained off treatment. The patient no longer needs daily medication. The long-term liver damage risk decreases substantially.
For 35 years, the hepatitis B field has been searching for a finite therapy that can achieve functional cure at meaningful rates. Two phase 3 trials published in the New England Journal of Medicine have now shown that a drug called bepirovirsen can do this in approximately one in five eligible patients, and the result was achieved in a rigorous, placebo-controlled, global trial design for the first time.
What We Know So Far
The B-Well 1 and B-Well 2 trials, conducted by the B-Well Study Group and sponsored by GSK (co-developer, alongside Ionis Pharmaceuticals), enrolled a combined total of 1,838 adults with noncirrhotic chronic hepatitis B infection across 29 countries, including sites in Europe, the Asia-Pacific region, and the Americas. Recruitment ran from December 2022 to May 2025.
Eligible patients had been receiving standard nucleos(t)ide analog (NA) antiviral therapy for at least 6 months, with hepatitis B surface antigen (HBsAg) levels between 100 and 3,000 IU/mL, and with HBV DNA below detectable thresholds, meaning these were virologically suppressed patients in whom background standard-of-care therapy had already reduced viral replication to minimal levels.
Patients were randomly assigned to receive subcutaneous weekly injections of bepirovirsen 300 mg (with loading doses on days 4 and 11) or a placebo for 24 weeks. At 72 weeks after therapy discontinuation, approximately 20% of bepirovirsen-treated patients achieved functional cure, defined as undetectable HBsAg and undetectable HBV DNA for at least 24 consecutive weeks after stopping all treatment.
In B-Well 1, 127 of 650 treated patients achieved functional cure (20%); in B-Well 2, 106 of 570 treated patients achieved it (19%). In the placebo group, zero patients in either trial achieved functional cure. The NEJM paper (DOI: 10.1056/NEJMoa2515131) was published May 28, 2026.
Where the Impact Is Highest
In the United States, approximately 1.9 million people live with chronic hepatitis B, disproportionately including people of Asian descent (particularly from China, Vietnam, Korea, and the Philippines), immigrants from sub-Saharan Africa, and individuals with a history of injection drug use or exposure to hepatitis B before childhood vaccination was routine.
Asian Americans account for more than half of all chronic hepatitis B cases in the United States despite being about 6% of the U.S. population, according to the Hepatitis B Foundation. Major metros with large Asian American communities, including the San Francisco Bay Area, Los Angeles, New York City, and Houston, carry the highest per-capita burden.
For patients with low baseline HBsAg levels (below 1,000 IU/mL), the functional cure rate was even higher in subgroup analyses: 25% to 28%, suggesting that patient selection based on baseline viral antigen levels could identify those most likely to benefit.
What Doctors and Experts Say
Dr. Seng Gee Lim, director of Hepatology at the National University Health System in Singapore and one of the B-Well trial's lead investigators, offered a careful but optimistic summary in AJMC reporting: "These phase 3 data represent a major step forward in the search for a finite treatment for chronic hepatitis B."
He added the important qualification in Medical News Today reporting: "Bepirovirsen is the first step towards functional cure, and this is hope for those living with hepatitis B — but better therapies will lead to higher cure rates in the future."
The 20% functional cure rate is not the endpoint most hepatitis B specialists would call definitive. The majority of patients do not achieve functional cure with bepirovirsen alone. Researchers are already investigating combination regimens pairing bepirovirsen with other agents to increase the proportion who respond.
What the Evidence Shows and What It Does Not
These are well-designed, double-blind, placebo-controlled phase 3 trials published in the most prestigious medical journal in the world. The evidence that bepirovirsen achieves functional cure in approximately 20% of eligible patients is strong.
What the evidence does not show is what happens to those patients beyond 72 weeks, whether functional cure is durable over the long term, and whether patients who achieved functional cure in the trial will face a lower risk of cirrhosis and hepatocellular carcinoma over decades. These outcomes are important but will take many more years of follow-up to assess.
The patient population in B-Well was carefully defined: noncirrhotic, virologically suppressed, with a specific HBsAg range. Patients with cirrhosis, HIV coinfection, or very high or very low viral antigen levels were excluded. How bepirovirsen performs in those populations remains unknown.
MedicalDaily Evidence Check
- Study type: Two identical phase 3, randomized, double-blind, placebo-controlled trials (B-Well 1: NCT05630807; B-Well 2: NCT05630820)
- Sponsor: GSK / Ionis Pharmaceuticals (B-Well Study Group)
- Published in: New England Journal of Medicine, May 28, 2026 (Volume 394, Issue 24, DOI: 10.1056/NEJMoa2515131); presented at EASL Congress 2026
- Participants: 1,838 adults with noncirrhotic chronic hepatitis B across 29 countries
- What it found: Approximately 20% functional cure rate (bepirovirsen) vs. 0% (placebo) at 72 weeks post-treatment; reduction in HBsAg production sustained off therapy
- What it did not prove: Durability of functional cure beyond 72 weeks; reduction in long-term cirrhosis or liver cancer risk; applicability in cirrhotic, HIV-coinfected, or high/low HBsAg patients
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What readers should know: Bepirovirsen is not yet approved; GSK has submitted regulatory applications in the U.S., Europe, Japan, and China; FDA Breakthrough Therapy and Fast Track designations have been granted; a first regulatory decision is anticipated later in 2026
Who Faces the Greatest Risk — and May Benefit Most?
People living with chronic hepatitis B who may be candidates for bepirovirsen if it is approved include:
- Adults with noncirrhotic chronic HBV infection who are virologically suppressed on current NA therapy but who have not achieved HBsAg loss
- People with moderate HBsAg levels (100 to 1,000 IU/mL) who may have the highest functional cure rates based on subgroup data
- Long-term NA therapy patients who prefer the possibility of a finite treatment course over indefinite daily medication
People who may not be candidates based on B-Well inclusion criteria include those with cirrhosis, HIV coinfection, or very low HBsAg levels.
Symptoms and Warning Signs to Watch For
Chronic hepatitis B is typically asymptomatic until significant liver damage has occurred. Warning signs of advanced liver disease that may indicate the need for evaluation include:
- Persistent fatigue and weakness
- Right-sided abdominal discomfort or swelling
- Jaundice (yellowing of the skin or whites of the eyes)
- Dark urine or pale-colored stools
- Easy bruising or unexplained bleeding
- Swelling of the legs or abdomen (ascites)
Anyone with chronic hepatitis B who develops these symptoms should seek medical evaluation promptly. Regular monitoring with liver enzyme tests, HBsAg levels, HBV DNA, and liver imaging is the standard of care for all patients with chronic HBV.
What You Can Do Now
- If you live with chronic hepatitis B, ask your gastroenterologist or infectious disease specialist about bepirovirsen at your next appointment. The drug is not yet approved, but understanding your eligibility criteria based on the B-Well trial population is a useful conversation to have now.
- Continue any prescribed NA therapy without interruption. Stopping standard antiviral treatment before alternative therapy is available and appropriate for your situation carries the risk of viral rebound and liver flare.
- Contact the Hepatitis B Foundation or Hepatitis B United for information on clinical trial opportunities, patient education, and community support resources.
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If you have never been tested for hepatitis B, particularly if you were born in a country with high HBV prevalence or have risk factors, ask your clinician for a hepatitis B blood panel.
Cost and Access: What Patients Should Know
Bepirovirsen is not yet approved and does not have a listed price. If regulatory approval is granted later in 2026 as GSK anticipates, pricing will depend on the final label, indicated population, and negotiated payer arrangements. Given the finite treatment duration (24 weeks), a single-course pricing model is possible rather than the long-term per-year pricing used for chronic NA therapy.
Clinical trials are still enrolling for related combination-therapy approaches. Patients interested in trial participation can search at ClinicalTrials.gov using the search term "bepirovirsen."
What Happens Next
GSK has submitted regulatory applications for bepirovirsen in the United States, Europe, Japan, and China, and anticipates initial regulatory decisions later in 2026. The FDA has granted Breakthrough Therapy and Fast Track designations, both of which expedite the review process.
Ongoing combination trials are testing bepirovirsen with other HBV-targeting agents in hopes of improving functional cure rates beyond 20%. The field is broadly optimistic that combination approaches may eventually achieve the 40% to 50%+ cure rates that would make functional cure a viable expectation for the majority of treated patients rather than a minority outcome.
The Bottom Line
Two replicate phase 3 trials published in the New England Journal of Medicine have shown that bepirovirsen, a 24-week subcutaneous treatment, can achieve functional cure in approximately one in five eligible patients with chronic hepatitis B — the first time a phase 3 trial has demonstrated this outcome at scale with a 0% cure rate in the placebo group. The drug is not yet approved, optimal patient selection is still being refined, and long-term durability is not yet known. But for the approximately 1.9 million Americans living with chronic hepatitis B, this is the most significant clinical trial result the field has seen in a generation.
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