FDA Fast Tracks GSK's Bepirovirsen for Chronic Hepatitis B Virus

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In clinical trials, bepirovirsen showed the potential to address a significant unmet medical need for patients with chronic hepatitis B by reducing hepatitis B surface antigen levels and HBV DNA.

Image credit: Destina | stock.adobe.com. Structural detail of Hepatitis B virus on blue-green background.

Image credit: Destina | stock.adobe.com.

The FDA has granted Fast Track designation to GSK’s novel antisense oligonucleotide (ASO) bepirovirsen to treat chronic hepatitis B (CHB).1 The drug was designed to specifically recognize the RNA used by hepatitis B virus (HBV) to replicate in infected liver cells. Bepirovirsen, a triple action investigational ASO, has been found to stimulate an immune response through Toll-like receptor 8, which helps the immune system achieve durable clearance of HBV from circulating blood.2

“Bepirovirsen is the only single agent in Phase III development that has shown the potential to achieve clinically meaningful functional cure response when combined with oral nucleoside/nucleotide analogues (NAs),” GSK stated in a press release.1

HBV is classified as a hepaDNA virus, made up of four distinct genomic regions with a complex mode of replication susceptible to the development of mutant forms of the virus. HBV is typically diagnosed by a hepatitis B surface antigen (HBsAg) test to detect active infection.3

Management of HBV typically involves preventive measures that seek to minimize active infection rates. One of the most effective strategies to achieve this is vaccination early in life.

For cases in which the virus is acquired by an infant from their mother, administration of hepatitis B immunoglobulin and the HBV vaccine within 24 hours of birth has been found effective.3 Beyond preventative actions, maintaining antibody levels is also of significant importance. Among patients with active HBV infection, interferon alfa is typically used to directly inactivate viral DNA by inhibiting protein synthesis.

In clinical trials, bepirovirsen showed the potential to address a significant unmet medical need for patients with HBV. The FDA based its Fast Track designation on findings from the Phase IIb B-Clear and B-Sure trials. The studies analyzed the efficacy, safety, and durability of response for bepirovirsen in patients with CHB.

In the B-Clear trial, bepirovirsen was found to lower HBsAg levels and HBV DNA following 24 weeks of treatment in patients with CHB.4 Investigators evaluated the efficacy and safety of 12- or 24-weeks treatment with bepirovirsen in patients with CHB on stable nucleoside/nucleotide analogues (NA) treatment or not on NA treatment with bepirovirsen at baseline.

Across both cohorts, virologic responses were observed at the end of the treatment. Among patients administered NA treatment, 24 weeks of 300 mg bepirovirsen produced HBsAg less than Lower Limit of Quantification (LLOQ) and HBV DNA less than LLOQ in 28%. Among patients not on NA, 300 mg bepirovirsen produced HBsAg less than LLOQ and HBV DNA less than LLOQ in 29%.4

The B-Sure trial is evaluating longer term efficacy and durability of response for participants from the B-Clear study for an additional 33 months. The trial includes criteria for halting NA treatment to analyze the potential to achieve a functional cure in those who successfully stop taking their medication while continuing to show no serologic evidence of HBsAg or HBV DNA.

References

1. GSK receives US FDA Fast Track designation for bepirovirsen in chronic hepatitis B. GSK. News release. February 12, 2024. Accessed February 12, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-us-fda-fast-track-designation-for-bepirovirsen-in-chronic-hepatitis-b/

2. Positive data for bepirovirsen from B-Clear phase IIb trial presented at American Association for the Study of Liver Diseases’ Meeting with simultaneous publication in the New England Journal of Medicine. GSK. November 8, 2022. Accessed February 12, 2024. https://www.gsk.com/en-gb/media/press-releases/positive-data-for-bepirovirsen-from-b-clear-phase-iib-trial/

3. Gregorio, Germana V, et al. Viral Hepatitis. National Center for Biotechnology Information, U.S. National Library of Medicine, 1995, https://www.ncbi.nlm.nih.gov/pmc/. Accessed February 12, 2024.

4. GSK presents promising new data for bepirovirsen, an investigational treatment for chronic hepatitis B. GSK. News release. June 25, 2022. Accessed February 12, 2024.

https://www.gsk.com/en-gb/media/press-releases/gsk-presents-promising-new-data-for-bepirovirsen-an-investigational-treatment-for-chronic-hepatitis-b/

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