GSK plc (LON:GSK, NYSE: GSK) has 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 Nrtl 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.[2] Bepirovirsen is a first in class antisense oligonucleotide (ASO) and offers unprecedented functional cure rates compared to current standard of care. The approval was granted under FDA priority review and Breakthrough Therapy Designation, recognising significant improvement of bepirovirsen and nucleos(t)ide analogue therapy over existing standard of care.[3]
Tony Wood, Chief Scientific Officer, GSK, said: “Despite current therapies, many people living with chronic hepatitis B remain on treatment indefinitely and continue to face the risk of serious liver complications.[4],[5] For the first time, with Hibsago, US patients have the potential to achieve functional cure after a six-month treatment course, with the added convenience of the option of self-administration after the first dose.”
The approval was supported by results from the B-WELL phase III trials showing functional cure rates of 19% in adults with ≤3000 IU/ml HBsAg, compared to current standard of care alone, which typically achieves less than 1% functional cure rate after one year of treatment.[6],[7] Functional cure occurs when HBV DNA and viral protein – HBsAg – are undetectable for at least 24 weeks after stopping all treatment, indicating the disease is controlled by the immune system without medication.[8]
Dr. Norah Terrault, Chief of Gastroenterology & 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.”
Dr. Chari Cohen, President of Hepatitis B Foundation, said: “CHB is a major public health challenge, affecting millions of people in the US and accounting for approximately 56% of all global liver cancer cases.1,[9] Today marks significant progress towards our aim of transforming the way CHB is managed with improvements in screening, diagnosis, and the availability of innovative treatment options for our community.”
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.
GSK continues to advance regulatory submissions for bepirovirsen across multiple geographies with key regulatory decisions anticipated in the coming months.
Results from the B-Well phase III trials
Pooled data from the B-Well phase III trials showed that six-month treatment with bepirovirsen achieved a clinically meaningful 19% functional cure response rate (233 of 1,220 vs. 0 of 614 in the placebo group). B-Well 1 and B-Well 2 each met the primary end point, demonstrating a statistically significant improvement in functional cure versus placebo in the overall study population (adults with ≤3000 IU/ml HBsAg level). In a key secondary endpoint, a functional cure rate of 26% (200 of 768 vs. 0 of 393 in the placebo group) was achieved in participants with ≤1000 IU/ml HBsAg level, a group that represents approximately 45% of diagnosed CHB cases globally.[10]
Exploratory analyses also showed bepirovirsen reduced HBsAg to ≤100 IU/ml in 49% of participants (598 of 1220) in the overall study population, and in 62% of bepirovirsen recipients in the ≤1000 IU/ml (476 of 768) sub-group[11] as of the week 72 visit. Medical literature has linked this low level of surface antigen with increased immune control and improved patient outcomes.[12],[13],[14]
The trials showed an acceptable safety and tolerability profile consistent with other studies of bepirovirsen. The three most frequently observed adverse events were injection site erythema, local pain and temporary rise in the blood level of a liver enzyme.
