Phase 3 Data Show Functional Cure Potential in Hepatitis B

Ionis Pharmaceuticals and its partner GSK have reported positive Phase 3 results for bepirovirsen, an investigational antisense oligonucleotide therapy for chronic hepatitis B (CHB), marking a significant development in the search for treatments capable of achieving a functional cure for the disease.

The findings, presented at the European Association for the Study of the Liver (EASL) Congress and simultaneously published in The New England Journal of Medicine, demonstrated that bepirovirsen achieved statistically significant and clinically meaningful functional cure rates in patients with chronic hepatitis B, a disease that affects hundreds of millions of people worldwide and currently requires long-term or lifelong treatment.

Bepirovirsen is designed to target hepatitis B virus (HBV) RNA, reducing viral replication and levels of hepatitis B surface antigen (HBsAg), a key marker of infection. The therapy is also believed to help restore immune control over the virus, potentially allowing patients to remain disease-free without ongoing medication.

The pivotal Phase 3 program consisted of two studies, B-Well 1 and B-Well 2. Combined data from both trials showed that 19% of patients receiving six months of treatment with bepirovirsen achieved a functional cure six months after discontinuing all therapy, compared with no patients in the placebo group. The primary endpoint was met with strong statistical significance in both studies.

Researchers also reported particularly encouraging results among patients with lower baseline hepatitis B surface antigen levels. In participants with HBsAg levels of 1,000 IU/mL or less—a population representing roughly 45% of diagnosed chronic hepatitis B cases globally—the functional cure rate increased to 26%, compared with zero in the placebo arm.

A functional cure is defined as the absence of detectable hepatitis B virus DNA and hepatitis B surface antigen in the blood for at least six months after treatment has ended. Achieving this outcome suggests that the body’s immune system is controlling the infection without the need for ongoing antiviral therapy.

The results compare favorably with current treatment standards, where functional cure rates generally remain below 1% despite years of therapy.

Additional exploratory analyses further highlighted the potential benefits of bepirovirsen. Nearly half of treated patients achieved very low hepatitis B surface antigen levels one year after completing therapy, a marker associated with stronger immune control and improved long-term outcomes. Furthermore, 23% of all treated patients maintained undetectable viral DNA levels at Week 72, compared with none of the patients receiving placebo.

The therapy also demonstrated a manageable safety profile. The most commonly reported adverse events were injection-site redness, localized pain, and temporary increases in liver enzyme levels. Investigators noted that the safety findings were generally consistent with previous studies of the drug.

Brett Monia, Chief Executive Officer of Ionis Pharmaceuticals, described the findings as a meaningful advance for patients living with chronic hepatitis B, emphasizing the lack of approved therapies capable of delivering functional cures. He noted that bepirovirsen’s mechanism of action positions it uniquely to suppress viral activity while enhancing immune system control of the infection.

The positive data come as bepirovirsen undergoes regulatory review in several major markets. The therapy is currently under Priority Review by the U.S. Food and Drug Administration and has received both Breakthrough Therapy and Fast Track designations. Regulatory submissions are also under review in Europe, Japan, and China, where the drug has received expedited review status.

GSK expects the first regulatory decisions during the third quarter of 2026 and has already begun launch preparations.

Bepirovirsen was licensed by GSK from Ionis in 2019 under a collaborative development agreement. If approved, the therapy could become one of the first treatments to offer a realistic path toward functional cure for chronic hepatitis B, potentially transforming care for millions of patients worldwide and addressing one of the most significant unmet needs in infectious disease medicine.