Ionis Pharmaceuticals announces data from GSK’s Phase 2b study of bepirovirsen

Ionis Pharmaceuticals (IONS) announced that GSK (GSK) presented positive end of study data from the Phase 2b B-Clear study of bepirovirsen, an investigational antisense oligonucleotide treatment for patients with chronic hepatitis B virus. The results showed that treatment with bepirovirsen resulted in sustained clearance of hepatitis B surface antigen and hepatitis B virus DNA for 24 weeks after end of bepirovirsen treatment in people with CHB. The study results were presented at the American Association for the Study of Liver Diseases’ The Liver Meeting in Washington, DC. The results from the B-Clear Phase 2b study provide initial evidence that bepirovirsen, as monotherapy or in combination with nucleoside/nucleotide analogue, can deliver sustained reductions in HBsAg and HBV viral DNA in specific patient groups. The full results from the study are now available in The New England Journal of Medicine. In treatment arm 1 of the study, 9% of patients on NA treatment and 10% of patients not on NA treatment achieved the primary outcome of HBsAg levels below the Lower Limit of Quantification and HBV DNA levels below the LLOQ, respectively. This is defined as a sustained response and was observed for 24 weeks post last dose. In the study, sustained response rates were higher in subjects with low baseline HBsAg than in those with high baseline HBsAg. Patients with low baseline hepatitis B surface antigen levels responded best to treatment with bepirovirsen with 16% and 25% of patients achieving the primary outcome in treatment arm 1 of the on NA and not on NA cohort, respectively. Currently, nucleoside/nucleotide analogues are the recommended first-line therapy for patients with chronic HBV because they can inhibit viral replication. However, they cannot clear the virus and are generally taken for life. Bepirovirsen is uniquely designed to reduce HBV replication and suppress HBsAg and stimulate innate immunity which could potentially lead to functional cure. Functional cure is largely defined as sustained, undetectable levels of HBV DNA and HBsAg in the blood with or without generating protective antibodies after a finite course of treatment. Functional cure occurs when the virus is not eliminated from the body but is at low levels that are undetectable in blood and can be controlled by the immune system without medication. GSK is exploring sequential treatment trials of bepirovirsen with other therapeutic modalities, with the aim of increasing functional cure rate in more patients and reducing the overall burden of CHB. These include Phase 2b study of bepirovirsen in sequential combination with pegylated interferon treatment; Phase 2 study of bepirovirsen in sequential combination with GSK’s chronic hepatitis B targeted immunotherapy.