Ionis Pharmaceuticals, Inc. announced that GSK presented positive end of study data from the Phase 2b B-Clear study of bepirovirsen (formerly IONIS-HBVRx), an investigational antisense oligonucleotide treatment for patients with chronic hepatitis B virus (CHB). The results showed that treatment with bepirovirsen resulted in sustained clearance of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) 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' (AASLD) 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 (NAs), can deliver sustained reductions in HBsAg and HBV viral DNA in specific patient groups. The full results from the study are now available in TheNew 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 (LLOQ) 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 (< 1000 IU/mL) than in those with high baseline HBsAg (>1000 IU/mL). 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 (PegIFN) treatment. Phase 2 study of bepirovirsen in sequential combination with GSK's chronic hepatitis B targeted immunotherapy. The B-Clear Phase 2b study is investigating the efficacy and safety of 12- or 24-weeks treatment with bepirovirsen in people living with CHB on stable NA treatment or not on NA treatment at study start.

The primary endpoints are the proportion of patients achieving HBsAg levels below the Lower Limit of Quantification (LLOQ), and HBV DNA levels below the LLOQ sustained for 24 weeks without rescue medication after end of treatment with bepirovirsen. The study consists of two parallel cohorts, one for patients receiving NA treatment and the other for patients who were not on NA. Patients from each arm were randomized to one of four treatment arms within each cohort, with treatment administered weekly with or without loading doses (LD) on days four and 11: Bepirovirsen 300 mg with LD for 24 weeks; Bepirovirsen 300 mg with LD for 12 weeks then 150 mg for 12 weeks; Bepirovirsen 300 mg with LD for 12 weeks then placebo for 12 weeks; Placebo with LD for 12 weeks then bepirovirsen 300 mg without LD for 12 weeks.

Hepatitis B virus infection is a serious health problem that can lead to significant and potentially fatal health conditions, including cirrhosis, liver failure and liver cancer. Chronic hepatitis B infection is caused by the hepatitis B virus and is a major global health concern, affecting nearly 300 million people worldwide.i,ii Chronic HBV infection is one of the most common persistent viral infections in the world. Currently available therapies, although effective in reducing circulating HBV DNA in the blood, do not efficiently inhibit HBV antigen production and secretion.