GSK's Hepatitis B Drug Bepirovirsen Achieves Functional Cure in 19% of Patients in Phase III Trials Published in NEJM

May 28, 2026 18:36 CST Updated 18:36

GSK

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Ionis Pharmaceuticals

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On May 28, 2026, the internationally leading medical journal *The New England Journal of Medicine* (NEJM) officially published the complete results of two pivotal Phase III studies from the B-Well series for bepirovirsen, GSK's innovative drug for chronic hepatitis B.Pivotal clinical data confirm that this antisense oligonucleotide (ASO) drug with a novel mechanism of action enables chronic hepatitis B patients receiving standard nucleos(t)ide analogue therapy to achieve19% functional cure rate, compared to the less than 1% cure rate of current standard clinical therapies, it achieves a nearly 20-fold improvement in therapeutic efficacy, marking a disruptive breakthrough in the field of chronic hepatitis B treatment over the past nearly 30 years.

Key clinical data: Nearly one-fifth of patients achieved functional cure of hepatitis B

Chronic hepatitis B is a major chronic disease posing a significant threat to global public health. With over 240 million infected individuals worldwide, it serves as the leading risk factor for primary liver cancer, imposing a heavy burden on global healthcare systems. Currently, mainstream clinical nucleos(t)ide analogues, such as entecavir and tenofovir, can only effectively suppress hepatitis B virus (HBV) replication and are unable to completely eradicate the virus. Consequently, patients require lifelong medication, and the probability of functional cure remains below 1%, leaving a substantial gap in clinical cure.

The recently announced global, multicenter Phase III clinical trials, B-Well 1 and B-Well 2, enrolled a total of 1,838 adult patients with chronic hepatitis B receiving stable standard-of-care therapy. The trials employed a standardized and scientifically rigorous study design: subjects received weekly injections of bepirovirsen or placebo for 24 weeks, followed by 24 or 48 weeks of standard maintenance therapy with nucleos(t)ide analogues. The functional cure endpoint was uniformly assessed at Week 72, yielding data that are highly rigorous and of significant clinical reference value.

Key efficacy data are as follows：

In the overall treated population, the bepirovirsen group19% of patients achieved standard functional cure, namely, sustained negative conversion of hepatitis B surface antigen (HBsAg) and serum HBV DNA reaching undetectable levels
In the favorable subgroup of patients with baseline hepatitis B surface antigen < 1000 IU/mL, the functional cure rate further increased to26%, demonstrates superior efficacy
No patients in the concurrent placebo group achieved a functional cure, fully confirming the core therapeutic value of the drug.

Professor Seng Gee Lim, Principal Investigator of this study and Head of the Department of Hepatology at National University Hospital, Singapore, commented: “No previous hepatitis B treatment regimen has ever achieved such a substantial cure rate. This marks a revolutionary leap in the history of chronic hepatitis B therapy.”

Unique Mechanism of Action: Triple-Target Breakthrough, Achieving Viral Clearance and Immune Reconstitution

Bepirovirsen is an innovative antisense oligonucleotide (ASO) therapeutic originally developed by Ionis Pharmaceuticals and exclusively licensed globally to GSK in 2019. Its triple synergistic mechanism of action, which distinguishes it from conventional therapies, serves as the cornerstone for achieving a breakthrough in hepatitis B cure, fundamentally overcoming the limitations of traditional treatments that merely suppress viral replication but fail to achieve viral clearance:

Potently Inhibits Viral Replication: Precisely degrades hepatitis B virus pregenomic RNA, blocks HBV DNA synthesis at the source, and disrupts the viral replication chain.

Complete Blockade of Antigen Expression: Targeted degradation of mRNA encoding hepatitis B surface antigen, significantly reducing HBsAg levels in patients and eliminating the basis for viral immune escape.

Activates the body's innate immunity: Exhibits immune-activating effects, effectively reverses HBV-induced host immune exhaustion, and restores endogenous antiviral immunity.

Dr. Melanie Paff, Head of HBV Drug Development at GSK, explicitly stated that immune activation is the core advantage enabling bepirovirsen to achieve a cure. Clinically, the hepatitis B virus continuously releases a large quantity of empty viral capsids as "immune decoys," which persistently exhausts immune cell function and prevents the immune system from recognizing and clearing infected hepatocytes. Bepirovirsen can simultaneously clear these viral decoys and activate the host immune response, enabling the body to autonomously eliminate the virus and achieve a cure.

Controllable Safety: Elevated ALT Is Not a Side Effect but a Marker of Drug Efficacy

Safety data showed that the incidence of grade ≥3 adverse events in the bepirovirsen treatment group was slightly higher than that in the placebo group. The most common adverse reaction was elevated alanine aminotransferase (ALT). Throughout the study, only 4 patients discontinued treatment due to ALT elevation. Overall, the safety profile was manageable and well tolerated.

Notably, global experts in the field of hepatology have reached a consensus: the ALT elevation observed in this trial is not merely a drug-related adverse effect, but rather a specific biomarker of therapeutic efficacy. Professor Lim explicitly stated: "Patients with elevated ALT generally exhibit a substantial decline in HBsAg and demonstrate a significantly higher probability of achieving a functional cure. This serves as a positive indicator of immune activation and viral clearance."

*The New England Journal of Medicine* published a concurrent editorial in which Professor Anna Lok of the University of Michigan Medical School further corroborated that in clinical practice, the risk of ALT elevation can be managed through standardized monitoring and the establishment of standardized thresholds for drug discontinuation. Compared with the breakthrough curative benefits conferred by the therapy, the overall risk is acceptable, demonstrating exceptionally high clinical utility.

Accelerating Global Regulatory Submissions, China Integrated into Core Launch Footprint

`Currently, GSK has simultaneously submitted to`United States, European Union, Japan, ChinaMarketing applications for bepirovirsen have been submitted across four core pharmaceutical markets, fully advancing the global commercialization of the drug. Notably, the U.S. FDA has granted Priority Review designation to the drug,The prescribed approval deadline (PDUFA) is October 2026., is expected to be the first to receive marketing approval in the United States.

Dr. Melanie Paff stated that the team is leveraging various accelerated review pathways to advance the drug's global commercialization, striving to break the dilemma of lifelong hepatitis B treatment as soon as possible and improve medication accessibility for patients worldwide.

Continuous R&D Iteration: Combination Therapy Builds Momentum Toward Higher Cure Rates

Despite bepirovirsen achieving a historic efficacy breakthrough in hepatitis B treatment, over 80% of patients still have not achieved a functional cure. In response, GSK has clearly defined its subsequent iterative R&D direction, focusing on combination therapy regimens to continuously improve cure rates and expand coverage to a broader patient population.

Currently, GSK is advancing a Phase II combination clinical trial of bepirovirsen and Johnson & Johnson’s siRNA drug, JNJ-3989. JNJ-3989 potently reduces patient HBsAg levels and demonstrates comparable efficacy in individuals with high baseline antigen loads. This clinical combination strategy first utilizes the siRNA agent to lower patients’ HBsAg levels into the optimal therapeutic window, followed by bepirovirsen to activate the immune response and clear the virus, ultimately forming a synergistic combination with curative potential.

In addition, GSK has established a comprehensive hepatitis B cure pipeline spanning multiple therapeutic modalities, including siRNA, PAPD5/7 inhibitors, and TLR8 agonists, while continuously advancing differentiated innovative therapies in a concerted effort to overcome the challenge of achieving an HBV cure.

Industry analysis indicates that the clinical breakthrough of bepirovirsen officially marks the transition of chronic hepatitis B treatment from "lifelong viral suppression and disease management" to a new era of "precision intervention and the pursuit of a cure." Although achieving a complete cure for hepatitis B still requires ongoing research and development, the commercial launch of this innovative drug will bring renewed hope to the 240 million hepatitis B patients worldwide, offering them the prospect of freedom from lifelong medication and the attainment of a clinical cure.

Information Source：https://www.fiercebiotech.com/biotech/gsks-hepatitis-b-drug-cures-one-fifth-patients-major-step-pervasive-disease

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