GSK/Ionis Hepatitis B ASO Therapy Bepirovirsen Receives FDA NDA Acceptance and Breakthrough Therapy Designation

Breakthrough Therapy Designation aims to expedite the review of drugs for serious or life-threatening conditions, where preliminary clinical evidence suggests a substantial improvement over existing therapies. This designation allows drug development programs to receive more guidance from the FDA. Priority Review status is granted to marketing applications for medicines that, if approved, would offer significant improvements in safety or effectiveness for treating, preventing, or diagnosing serious diseases. The FDA aims to take action within six months, compared to the standard review time of ten months. Bepirovirsen also received Fast Track designation from the U.S. FDA in February 2024.

CHB is a major public health challenge, affecting more than 250 million people globally and 1.7 million in the United States. Current standard treatment regimens, typically nucleos(t)ide analogs, usually require lifelong therapy, with functional cure rates remaining low, generally around 1%. A functional cure refers to the undetectable levels of hepatitis B virus DNA and viral proteins (hepatitis B surface antigen, HBsAg) in the blood for at least 24 weeks after stopping all treatments, indicating that the disease can be controlled by the immune system without medication. Achieving a functional cure is associated with a significantly reduced risk of long-term liver complications, including liver cancer.

The regulatory submission and Breakthrough Therapy Designation were supported by positive results from the Phase 3 clinical trials, B-Well 1 and B-Well 2. In these trials, bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate. Across all hierarchical endpoints, the functional cure rate in the bepirovirsen plus standard-of-care group was significantly higher than that in the standard-of-care alone group, with an even greater effect observed in patients with lower baseline HBsAg levels. Bepirovirsen exhibited an acceptable safety and tolerability profile, consistent with previous studies. The data will be presented at the European Association for the Study of the Liver (EASL) 2026 Congress in May 2026 and is planned for simultaneous publication in a peer-reviewed scientific journal in 2026.

GSK obtained the license for bepirovirsen from Ionis in 2019 under a collaboration development and licensing agreement. Under the terms of the agreement, Ionis has received upfront payments, licensing fees, and development and regulatory milestone payments, and is eligible to receive additional regulatory and sales milestone payments, as well as tiered royalties ranging from 10% to 12% based on bepirovirsen's net sales.

Bepirovirsen is currently under review by the European Medicines Agency (EMA), China's National Medical Products Administration (NMPA), and Japan's Ministry of Health, Labour and Welfare (MHLW). The drug has also been granted Breakthrough Therapy Designation in China and received the "SENKU Designation" (Pioneer Review Designation) in Japan.

About B-Well 1 and B-Well 2 Studies

B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) are multicenter, randomized, double-blind, placebo-controlled trials conducted across 29 countries globally. These trials evaluated the efficacy, safety, pharmacokinetic profile, and durability of functional cure in participants with chronic hepatitis B who were receiving nucleos(t)ide analog (NA) therapy and had baseline surface antigen (HBsAg) ≤3000 IU/ml. The primary endpoint assessed the proportion of participants achieving functional cure among those 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 undetectable levels of HBsAg in the blood for at least 24 weeks after stopping all treatments, 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, leading to long-term infection, affecting over 250 million people globally. The disease causes approximately 1.1 million deaths worldwide each year. Many patients often require lifelong antiviral therapy to suppress the virus; thus, achieving a functional cure is a key goal in disease management.

About Bepirovirsen

Bepirovirsen is an investigational antisense oligonucleotide (ASO) designed to recognize and inhibit the production of genetic components (i.e., RNA) of the hepatitis B virus that can cause chronic disease, potentially allowing the human immune system to regain control. Bepirovirsen can reduce the production of HBV-related RNA and viral proteins, suppress the levels of hepatitis B surface antigen (HBsAg) in the blood, and stimulate the immune system to increase the chances of achieving a durable and sustained response.

About Ionis Pharmaceuticals

For thirty years, Ionis has been dedicated to inventing drugs that create a better future for patients suffering from severe diseases. Ionis already has marketed drugs and a leading R&D pipeline in the fields of neurology, cardiometabolic diseases, and other areas with urgent patient needs. As a pioneer in RNA-targeted therapies, in addition to advancing new approaches in gene editing, Ionis continues to drive innovation in RNA therapeutics. Our deep understanding of disease biology, industry-leading technology, and our passion and urgency to bring life-changing therapies to patients collectively propel our work forward.

Source:

1.Ionis