Breakthrough Drug Offers Functional Cure for Hepatitis B

Scientists have achieved a major breakthrough in the treatment of chronic hepatitis B, with a new drug demonstrating the ability to cure one in five patients in landmark Phase III clinical trials. The results, published May 28 in the New England Journal of Medicine, represent the most significant advance against the virus in decades and could transform the lives of the 254 million people worldwide living with the chronic infection.

The investigational drug, bepirovirsen, is a first-in-class antisense oligonucleotide (ASO) developed by Ionis Pharmaceuticals and licensed to GSK. In the B-Well 1 and B-Well 2 trials — global, randomized, double-blind, placebo-controlled studies conducted across 29 countries involving 1,838 adults — approximately 19% of participants achieved a “functional cure,” meaning their immune systems controlled the virus without medication for at least 24 weeks after stopping all treatment. Among patients with the lowest baseline levels of the hepatitis B surface antigen, the functional cure rate reached 26%, according to National Geographic.

The Challenge of Hepatitis B

Hepatitis B is a viral infection that attacks the liver and is the leading cause of liver cancer worldwide. The World Health Organization estimates that 254 million people were living with chronic hepatitis B in 2022, with 1.2 million new infections and approximately 1.1 million deaths each year — mostly from cirrhosis and liver cancer. The virus is often called a “silent killer” because 50-70% of people with acute infection show no symptoms, and only 13% of infected individuals are aware of their status.

Current standard of care — nucleos(t)ide analogues such as tenofovir and entecavir — requires lifelong daily therapy and achieves functional cure in only about 1-3% of patients after 8-10 years of treatment. Pegylated interferon-alpha offers higher cure rates but comes with significant side effects that make it difficult to tolerate.

How Bepirovirsen Works

Bepirovirsen is an antisense oligonucleotide — a short, synthetic strand of DNA-like molecules that bind to the virus’ genetic material. It has a triple mechanism of action: it inhibits viral replication, suppresses hepatitis B surface antigen (HBsAg) levels in the blood, and stimulates the immune system. After injection, the drug is taken up by macrophages — specialized white blood cells — functioning as an immunomodulator that allows the immune system to regain control of the infection.

“We’ve not had a treatment come close to this level of cure,” said Seng Gee Lim, study co-author and director of hepatology at the National University Health System, Singapore, as reported by National Geographic. “I think my patients will be extremely delighted to have this treatment available.”

Expert Reactions

Independent experts have welcomed the results with cautious optimism. Anna Suk-Fong Lok, director of clinical hepatology at the University of Michigan Medical School, said in an editorial commentary accompanying the NEJM publication: “After many failed trials in the last 10 years, the B-Well Trials’ results provide hope that functional cure for hepatitis B is feasible.”

Tony Wood, chief scientific officer at GSK, stated that if approved, bepirovirsen “has the potential to transform treatment goals for people living with chronic hepatitis B by achieving significant functional cure rates — a first for the disease,” as BioSpace reported.

Regulatory Path and Access Concerns

GSK has submitted data to regulatory agencies in the United States, Canada, Europe, Japan, and China. Japan granted SENKU designation for expedited review, the U.S. Food and Drug Administration granted Fast Track designation, and China granted Breakthrough Therapy designation. Approval decisions are expected later in 2026, according to a GSK press release.

However, experts caution that significant questions remain about affordability and access. Geoff Dusheiko, a hepatologist at the Royal Free Hospital and University College London, noted that substantial numbers of patients live in resource-poor regions, and it is not clear how affordable or accessible bepirovirsen would be for them. The disease disproportionately affects sub-Saharan Africa and parts of Asia, where healthcare infrastructure is limited.

Limitations and Next Steps

The trial results cannot be generalized to patients with cirrhosis, HIV coinfection, or severe disease — these groups were excluded from the studies. The drug also worked best in patients whose hepatitis B was already better controlled, reinforcing the need for early diagnosis. Side effects include potential impacts on platelet counts and renal function, plus injection site reactions.

Jane Davies, an infectious disease specialist at the Royal Darwin Hospital in Australia and director of Hepatitis Australia, emphasized that the immediate priority remains unchanged: “Find people living with hepatitis B, connect them with culturally safe care, and support them before liver disease or liver cancer develops. This does not have to remain a silent epidemic.”

What’s Next

If approved, bepirovirsen could transform the treatment paradigm from lifelong viral suppression to finite-duration cure, potentially reducing liver cancer incidence and helping the WHO move toward its 2030 hepatitis elimination targets. Additional studies are needed for excluded patient populations, and researchers are exploring sequential treatment strategies combining bepirovirsen with other drugs to expand cure rates to broader patient populations. Pricing and access negotiations, especially for low- and middle-income countries, will be critical to determining the drug’s global impact.