Ionis Pharmaceuticals recently announced that the US Food and Drug Administration (FDA) has approved Hibsago (bepirovirsen) for the treatment of Chronic Hepatitis B (CHB) virus infection in combination with nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy in adult patients without cirrhosis, receiving NrtI therapy for at least 6 months, who have suppressed HBV deoxyribonucleic acid (DNA), and with hepatitis B virus (HBV) surface antigen (HBsAg) levels ≤3000 IU/ml, as determined by an FDA-authorised test. GSK licensed bepirovirsen from Ionis and collaborated with them on its development.

Bepirovirsen is a first in class RNA-targeted medicine that offers unprecedented functional cure rates compared to current Standard of Care (S0C). The approval was granted under FDA priority review and Breakthrough Therapy Designation (BTD), recognising significant improvement of bepirovirsen and nucleos(t)ide analogue therapy over existing SoC.

Brett P Monia, PhD, Chief Executive Officer, Ionis, said, “About 1.7 million people in the US are living with CHB, and yet treatment options have been historically limited and the vast majority of people living with the chronic infection require lifetime care without achieving meaningful functional cure. We are pleased to see the FDA approval of Hibsago, which adds to a growing portfolio of transformative medicines discovered and developed by Ionis that address serious diseases, including many that previously had limited or no available treatment options. We believe Hibsago will bring new hope to people living with Chronic Hepatitis B, offering the potential to achieve unprecedented functional cure rates after a 6-month treatment course.”

The approval was supported by results from the phase 3 B-well trials showing functional cure rates of 19 percent in adults with ≤3000 IU/ml HBsAg, compared to current SoC alone, which typically achieves less than 1 percent functional cure rate after 1 year of treatment. Functional cure occurs when HBV DNA and HBsAg are undetectable for at least 24 weeks after stopping all treatment, indicating the disease is controlled by the immune system without medication.

Norah Terrault, MD, MPH, FAASLD, Chief of Gastroenterology and Hepatology, USC Keck Medical Centre, said, “This is the start of a new era in treating people living with CHB. Bepirovirsen offers patients the potential to achieve functional cure after a short period of treatment, a long-standing goal for patients and physicians alike."

Quantitative surface antigen testing will support the diagnosis and identification of patients suitable for treatment with bepirovirsen who have baseline HBsAg levels ≤3000 IU/ml. Several tests are available, including a recently authorised FDA test.

Chari Cohen, DrPH, MPH, President, Hepatitis B Foundation, said, “CHB is a major public health challenge, affecting millions of people in the US and accounting for approximately 56 percent of all global liver cancer cases. Today marks significant progress toward our aim of transforming the way CHB is managed with improvements in screening, diagnosis, and the availability of innovative treatment options for our community.”

GSK continues to advance regulatory submissions for bepirovirsen across multiple geographies with key regulatory decisions anticipated in the coming months.

GSK licensed bepirovirsen from Ionis in 2019 under a collaborative development and licensing agreement. Under the terms of the agreement, Ionis has received an upfront payment, license fee and development and regulatory milestone payments and is eligible to receive additional regulatory and sales milestone payments as well as tiered royalties of 10-12 percent on net sales of bepirovirsen.