Bepirovirsen advances to regulatory review by the European Medicines Agency as a promising first-in-class therapy for chronic hepatitis B
GSK plc has announced a significant regulatory milestone as the European Medicines Agency (EMA) has formally accepted for review its marketing authorisation application (MAA) for bepirovirsen, an investigational antisense oligonucleotide (ASO) therapy. The submission seeks approval for the use of bepirovirsen in treating adults living with chronic hepatitis B (CHB), a condition that continues to pose a major public health challenge across Europe and globally.
Chronic hepatitis B is a long-term viral infection that affects the liver and can lead to severe complications, including cirrhosis, liver failure, and hepatocellular carcinoma. Despite the availability of antiviral therapies, the disease remains widespread. In Europe alone, approximately 3.2 million individuals are estimated to be living with CHB, underscoring the urgent need for more effective and potentially curative treatment options. The burden of the disease extends beyond regional borders, as CHB is a leading contributor to liver cancer worldwide, accounting for roughly 56% of global cases.
The current standard of care for CHB primarily involves the use of nucleos(t)ide analogues, antiviral medications that suppress viral replication. While these therapies are effective at controlling the virus, they rarely eliminate it entirely. As a result, most patients require lifelong treatment to maintain viral suppression. One of the key limitations of existing therapies is the very low rate of functional cure, typically around 1%. A functional cure is defined as the sustained absence of detectable hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) in the bloodstream for at least 24 weeks after discontinuation of treatment. Achieving this state indicates that the patient’s immune system has gained control over the virus without the need for ongoing medication.
Bepirovirsen represents a novel therapeutic approach designed to address these unmet needs. As an antisense oligonucleotide, it works by targeting the viral RNA, thereby reducing the production of viral proteins, including HBsAg. By lowering the levels of these proteins, bepirovirsen aims to restore the immune system’s ability to recognize and combat the virus more effectively, potentially leading to sustained viral control or even a functional cure.
The EMA’s acceptance of the MAA is based on compelling clinical evidence from two pivotal Phase III studies, B-Well 1 and B-Well 2. Both trials successfully met their primary endpoints, demonstrating that bepirovirsen achieved statistically significant and clinically meaningful improvements in functional cure rates compared with the current standard of care alone. Patients who received bepirovirsen in combination with standard antiviral therapy showed markedly higher rates of functional cure, highlighting the potential of this investigational therapy to transform the treatment landscape for CHB.
Importantly, the trials also demonstrated consistent efficacy across multiple predefined and ranked secondary endpoints, reinforcing the robustness of the findings. A particularly notable outcome was observed in a subgroup of patients with baseline hepatitis B surface antigen levels at or below 1000 IU/ml. In this population, the therapeutic effect of bepirovirsen was even more pronounced, suggesting that certain patient groups may derive enhanced benefit from the treatment.
Safety and tolerability are critical considerations in the development of any new therapy, especially for chronic conditions that may require long-term management. In the B-Well studies, bepirovirsen exhibited an acceptable safety and tolerability profile, consistent with observations from earlier-stage clinical trials. This consistency provides additional confidence in the overall benefit-risk profile of the therapy as it advances through the regulatory review process.
The acceptance of the MAA by the EMA marks the beginning of a comprehensive scientific evaluation of bepirovirsen’s efficacy, safety, and quality. If approved, the therapy could represent a significant advancement in the management of chronic hepatitis B, offering patients a realistic possibility of achieving a functional cure rather than relying on indefinite viral suppression.
Looking ahead, GSK plc plans to further share detailed findings from the B-Well 1 and B-Well 2 trials with the scientific community. The data are expected to be presented at a major medical congress and submitted for publication in peer-reviewed journals in 2026. These disclosures will provide deeper insights into the clinical performance of bepirovirsen and help inform physicians, researchers, and policymakers about its potential role in future treatment strategies.
In summary, the EMA’s acceptance of the bepirovirsen application represents a promising step forward in the effort to address the global burden of chronic hepatitis B. With its innovative mechanism of action and encouraging late-stage clinical results, bepirovirsen has the potential to redefine treatment goals by moving closer to achieving functional cures for patients living with this persistent and life-threatening disease.
About chronic hepatitis B
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 globally4, including an estimated 15,000 in Europe.1 Many patients require lifelong antiviral therapy for viral suppression, making functional cure a critical goal in disease management. The European Association for the Study of the Liver (EASL) guidelines identify functional cure as the ultimate goal of treatment.5
About bepirovirsen
Bepirovirsen is a triple action investigational antisense oligonucleotide (ASO), designed to recognise and orchestrate the destruction of the genetic components (i.e. mRNA and pregenomic RNA) of the hepatitis B virus that can lead to chronic disease, potentially allowing a person’s immune system to regain control. Bepirovirsen inhibits the replication of the viral genome in the body, 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 B-Well Clinical trial programmes
B-Well 1 and B-Well 2 trials are global multi-centre, randomised, 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 CHB and baseline surface antigen (HBsAg) ≤3000 IU/ml. The primary endpoint assessed the proportion of participants achieving functional cure in patients with baseline surface antigen (HBsAg) ≤3000 IU/ml. A key ranked secondary endpoint evaluated functional cure in participants with baseline HBsAg ≤1000 IU/ml. Functional cure is defined as hepatitis B surface antigen (HBsAg) loss and undetectable HBV DNA for at least 24 weeks after a finite course of treatment.
Bepirovirsen is also being evaluated as a potential backbone therapy for future sequential treatment strategies aimed at expanding functional cure to broader patient populations.
GSK licensed bepirovirsen from Ionis Pharmaceuticals and collaborated with them on its development. Bepirovirsen is currently not approved anywhere in the world.
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