GSK Reports U.S. Food and Drug Administration Grants Breakthrough Therapy Designation and Priority Review Acceptance for Bepirovirsen in Chronic Hepatitis B as Potential First-in-Class Treatment
Ionis Pharmaceuticals and its partner GSK have reached a significant regulatory milestone in the development of bepirovirsen, an investigational antisense oligonucleotide (ASO) being evaluated as a potential functional cure therapy for chronic hepatitis B (CHB). The U.S. Food and Drug Administration (FDA) has officially accepted the New Drug Application (NDA) for bepirovirsen and granted it Priority Review, alongside Breakthrough Therapy designation. The agency has also assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 26, 2026, marking a critical step toward potential approval in the United States.
The regulatory progress positions bepirovirsen as one of the most closely watched investigational therapies in the hepatitis B space, a field where treatment innovation has remained relatively stagnant for decades. According to Brett P. Monia, Ph.D., chief executive officer of Ionis Pharmaceuticals, the designation reflects both the strength of the clinical data and the potential impact of the therapy. He emphasized that more than one million individuals in the United States and over 250 million people globally are currently living with chronic hepatitis B, most of whom require lifelong antiviral therapy to keep the virus suppressed.
Monia highlighted that bepirovirsen represents a fundamentally different therapeutic approach compared to existing treatments. Unlike standard nucleos(t)ide analogues, which primarily suppress viral replication without eliminating the underlying infection, bepirovirsen is designed to target multiple components of the hepatitis B virus lifecycle. It reduces viral replication, suppresses hepatitis B surface antigen (HBsAg), and may help restore immune system activity against infected cells. This multimodal mechanism is central to its potential to achieve what is known as a functional cure.
A functional cure in hepatitis B is defined as sustained undetectable levels of both hepatitis B virus DNA and HBsAg in the blood for at least 24 weeks after discontinuation of all therapy. Achieving this outcome would represent a major advancement over current treatment paradigms, which typically require indefinite therapy and achieve functional cure rates of approximately 1% in most patient populations. The ability to discontinue treatment while maintaining viral suppression is considered a transformative goal in hepatology, as it could significantly reduce the long-term burden of disease management and associated healthcare costs.
The global burden of CHB remains substantial. In addition to its high prevalence, chronic infection is associated with serious long-term complications, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. These outcomes make hepatitis B one of the leading causes of liver-related mortality worldwide. As a result, therapies capable of altering disease progression or achieving sustained remission are viewed as high-priority targets for both regulatory agencies and public health organizations.
The FDA’s Breakthrough Therapy designation granted to bepirovirsen is intended to accelerate the development and review process for medicines that demonstrate early clinical evidence of substantial improvement over existing therapies for serious or life-threatening conditions. This designation provides enhanced interaction with the FDA, allowing for more frequent guidance on clinical trial design and regulatory strategy. In addition, Priority Review shortens the FDA’s standard review timeline from 10 months to approximately six months for eligible applications, reflecting the agency’s recognition of the therapy’s potential impact.
Bepirovirsen had previously received Fast Track designation in February 2024, further underscoring the regulatory interest in accelerating its development. Together, these designations indicate strong alignment between the sponsor and regulatory authorities regarding the urgency of addressing unmet medical needs in chronic hepatitis B.
The NDA submission and Breakthrough Therapy designation are supported by data from the Phase 3 B-Well 1 and B-Well 2 clinical trials. These studies demonstrated statistically significant and clinically meaningful functional cure rates in patients receiving bepirovirsen in combination with standard of care compared to standard therapy alone. Importantly, the benefit was observed across all ranked endpoints, with particularly strong responses in patients who had lower baseline levels of HBsAg. This subgroup analysis suggests that patient selection may play a role in optimizing treatment outcomes in future clinical use.
Safety and tolerability findings from the trials were generally consistent with earlier-stage studies. Bepirovirsen demonstrated an acceptable safety profile, with adverse events manageable within the clinical setting. These results are particularly important given the chronic nature of hepatitis B treatment, where long-term tolerability is a key consideration in therapy selection.
The clinical data supporting bepirovirsen will be presented at the upcoming European Association for the Study of the Liver (EASL Congress 2026) in May 2026. In addition, the results are expected to be submitted for publication in a peer-reviewed scientific journal, further contributing to the body of evidence surrounding antisense oligonucleotide-based therapies in infectious disease.
From a strategic perspective, bepirovirsen is the result of a long-standing collaboration between Ionis and GSK. Under a licensing agreement established in 2019, Ionis received upfront payments, licensing fees, and development milestone payments. The company remains eligible for additional regulatory and commercial milestone payments, as well as tiered royalties ranging from 10% to 12% on net sales, if the therapy is approved and successfully commercialized.
Beyond the United States, bepirovirsen is currently under regulatory review in multiple global markets, including the European Medicines Agency (EMA), the China National Medical Products Administration (NMPA), and Japan’s Ministry of Health, Labour and Welfare (MHLW). The therapy has also received Breakthrough Therapy designation in China and SENKU designation in Japan, reflecting international recognition of its potential clinical value.
Taken together, these developments mark bepirovirsen as a potentially transformative therapy in the treatment landscape for chronic hepatitis B. If approved, it could represent one of the first treatments capable of delivering functional cure in a meaningful proportion of patients, potentially reshaping long-standing treatment paradigms and reducing the global burden of disease.
About B-Well 1 and B-Well 2
B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) trials are global multi-center, randomized, double-blind, placebo-controlled trials conducted in 29 countries. They assessed the efficacy, safety, pharmacokinetic profile, and the durability of functional cure in nucleos(t)ide analogue (NA)-treated participants with chronic hepatitis B and baseline surface antigen (HBsAg) ≤3000 IU/ml. The primary endpoint assessed the proportion of participants achieving functional cure in patients with baseline HBsAg ≤3000 IU/ml.
A key secondary endpoint evaluated functional cure in participants with baseline HBsAg ≤1000 IU/ml. Functional cure is defined as HBsAg being undetectable in the blood for at least 24 weeks after stopping all treatment, indicating that the disease is controlled by the immune system without medication.
About Chronic Hepatitis B (CHB)
Hepatitis B is a viral infection that can cause both acute and chronic liver disease. Chronic hepatitis B occurs when the immune system is unable to clear the virus, resulting in long-lasting infection that affects more than 250 million people worldwide. The disease causes approximately 1.1 million deaths each year globally. Many patients often require lifelong antiviral therapy for viral suppression; making functional cure a critical goal in disease management.
About Bepirovirsen
Bepirovirsenis an investigational antisense oligonucleotide (ASO) designed to recognize and inhibit the production of the genetic components (i.e. RNA) of the hepatitis B virus that can lead to chronic disease, potentially allowing a person’s immune system to regain control. Bepirovirsen reduces the production of RNA and viral proteins associated with HBV, suppresses the level of hepatitis B surface antigen (HBsAg) in the blood, and stimulates the immune system to increase the chances of a durable and sustained response.
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis has marketed medicines and a leading pipeline in neurology, cardiometabolic and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients.
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