A Functional Cure for Hepatitis B Is Within Reach. Whether It Reaches Patients Is Not Yet Decided.

On May 28, 2026, the New England Journal of Medicine published results from two replicate phase 3 trials showing that a six-month course of an injectable drug, added to standard antiviral therapy, produced a functional cure in roughly one in five people living with chronic hepatitis B. The B-Well 1 and B-Well 2 trials, presented the same week at the European Association for the Study of the Liver (EASL) congress in Barcelona, enrolled 1,838 patients across 29 countries between December 2022 and May 2025. A functional cure was reported in 20% of patients receiving bepirovirsen in B-Well 1 and 19% in B-Well 2, compared with none of the patients who received placebo. For a disease that has required daily, lifelong treatment, the prospect of a finite therapy that lets patients stop taking medication is a meaningful shift.

Why a Functional Cure Has Been So Hard to Reach

A functional cure means hepatitis B surface antigen (HBsAg) loss and an unquantifiable hepatitis B virus (HBV) DNA level sustained for at least 24 weeks after a fixed course of therapy. The distinction matters because surface antigen loss is associated with better clinical outcomes than viral suppression alone, including a lower risk of liver cancer and minimal risk of relapse off treatment.

Current treatments rarely deliver it. As hepatologist Anna Lok of the University of Michigan notes in her accompanying editorial, nucleoside and nucleotide analogue (NA) therapy produces surface antigen loss in about 3% of patients after 8 to 10 years, and pegylated interferon reaches 8 to 11% after three years but is seldom used because of its side effects. Fewer than 1% of patients on existing drugs can control the virus after stopping treatment. That gap is why the field has spent years pursuing a cure, and why these results drew attention.

The burden falls unevenly. The Centers for Disease Control and Prevention (CDC) estimates roughly 640,000 to 660,000 people are living with chronic hepatitis B in the United States, though advocacy and clinical sources put the figure as high as 2.2 million. Asian American and Pacific Islander communities carry close to half the domestic burden despite making up about 6% of the population, and experience the highest hepatitis B-related mortality of any racial or ethnic group. African immigrant communities are also disproportionately affected. These are largely immigrant populations, many uninsured or underinsured, a fact that shapes everything about how a new therapy will or will not reach them.

What the Trials Showed

The B-Well trials randomly assigned patients 2:1 to receive 300 mg of subcutaneous bepirovirsen weekly or placebo for 24 weeks. All patients were on stable NA therapy and had a baseline HBsAg level between 100 and 3,000 IU per milliliter. Eligible patients discontinued NA therapy at week 48, and the primary outcome was assessed at week 72. At week 48, 24% of bepirovirsen patients in each trial met the criteria to stop background therapy, against none in the placebo groups.

The benefit tracked closely with baseline surface antigen levels. Among patients entering with the lower HBsAg level (1,000 IU per milliliter or less), functional cure reached 25% in B-Well 1 and 28% in B-Well 2. Among those in the higher stratum, rates fell to 10% and 5%. In a pooled analysis, the functional cure rate climbed to 26% among patients with the lowest baseline antigen levels, and sustained off-treatment viral suppression reached 31% in that group. Among the patients who achieved a functional cure, surface antibody developed in roughly two-thirds, a marker of durable immune control.

The Boundaries of the Evidence

The results are real, and they are bounded. As Lok cautions, they cannot be generalized to patients excluded from the trials: those with cirrhosis, HIV coinfection, or a baseline HBsAg level above 3,000 IU per milliliter. Patients positive for hepatitis B e antigen made up only 8% of enrollees, and functional cure occurred in just 11% and 5% of them. The trial authors acknowledge small numbers of Black and Hispanic or Latino patients, limiting what the data can say about those groups.

Safety requires attention. Adverse events of grade 3 or higher occurred in 16% of bepirovirsen patients versus 3% on placebo, with elevated alanine aminotransferase (ALT) the most common at 6%, and injection-site reactions affecting 53% of treated patients. Lok points out that several of these effects can become serious without stringent monitoring every one to two weeks and strict adherence to the protocol's rules for pausing therapy. That monitoring requirement is itself an access question. It presumes the kind of consistent clinical follow-up that under-resourced and uninsured patients often cannot count on.

Durability also remains open. Off-treatment follow-up in the B-Well trials is ongoing, with results scheduled through week 96. Smaller phase 2 data showed suppression for up to three years in more than 90% of functionally cured patients, but whether a bepirovirsen-induced cure lasts a lifetime is unproven.

The Access Question Is the Whole Question

A therapy that does not reach patients does not advance elimination. The World Health Organization estimates that only 13% of people living with hepatitis B worldwide know their status, and fewer than 5% of those diagnosed receive treatment. In the United States, research suggests up to 80% of people with chronic hepatitis B may be undiagnosed, and historically fewer than 50,000 have been receiving antiviral treatment.

Eligibility compounds the problem. The trials selected for patients with low, quantified surface antigen levels, and the authors stress that broader use of quantitative HBsAg testing will be essential to identify who can benefit. That test is not routine in much of U.S. practice today.

The regulatory clock is moving. The FDA has accepted GSK's application for priority review, granted Breakthrough Therapy designation, and set a target action date of October 26, 2026, with filings also underway in the European Union, Japan, China, and Canada. Approval determines whether the drug exists on the U.S. market. Coverage determines whether patients can use it. For a finite course of a specialty injectable, the decisions that will gate access are how commercial plans and Medicaid place the drug on formulary, what prior authorization and step-therapy requirements they attach, and whether the populations most affected domestically, many of them covered through Medicaid or uninsured, sit inside or outside those coverage decisions.

Turning a Milestone Into Elimination

Bepirovirsen gives us the first finite hepatitis B therapy with clinically meaningful cure rates in global phase 3 testing. Converting that into population-level progress toward viral hepatitis elimination depends on decisions still being made.

The CDC and state health departments should expand quantitative HBsAg testing and fund the chronic hepatitis B surveillance system, which remains under-resourced, so eligible patients can be found and the care cascade measured. The FDA should complete its review on schedule with labeling that supports the monitoring these data require. Commercial insurers and state Medicaid programs should commit to covering a functional cure without prior authorization barriers or step-therapy hurdles that would force patients to fail other approaches first, recognizing that a finite course replacing decades of daily NA therapy carries long-term value the standard pharmacy-benefit math tends to miss. Congress and the Department of Health and Human Services should fund the diagnosis-to-treatment infrastructure in the Viral Hepatitis National Strategic Plan so that a finite therapy reaches the under-screened immigrant communities where hepatitis B concentrates.

The science has done its part. We now have to decide whether the people who need this cure will be able to get it.