Nucleic acid drugs can achieve functional cure for hepatitis B

Hepatitis B is a major global public health issue caused by hepatitis B virus (HBV) infection. More than 300 million people worldwide are currently infected with HBV, and around 600,000 people die each year from hepatitis B-related liver disease or cancer.

Current therapies for chronic hepatitis B include nucleoside analogs (to limit viral replication) and interferons (to stimulate the immune system), but only a tiny percentage of patients can obtain a functional cure with a combination of the two.

Functional cure of hepatitis B is defined as remaining HBsAg (hepatitis B surface antigen) negative, undetectable hepatitis B virus DNA, normal liver biochemistry, and improved liver histopathology after stopping treatment.

Pharmaceutical giant GlaxoSmithKline (GSK) recently presented interim data from a Phase 2b clinical trial of its antisense oligonucleotide (ASO) drug bepirovirsen for the treatment of hepatitis B at the International Liver Congress 2022. The data show that after 24 weeks of treatment, nearly 30% of hepatitis B patients had undetectable levels of hepatitis B virus in their bodies, marking a major step forward for GSK toward achieving a functional cure for hepatitis B patients at this time.

Nucleoside/nucleoside analogs are the first-line treatment for patients with hepatitis B. They can inhibit the replication of the hepatitis B virus. They do not, however, destroy the hepatitis B virus and must thus be taken regularly for life. Bepirovirsen is a medicine that is specifically developed to limit hepatitis B virus replication and inhibit HBsAg generation, resulting in a functional cure and freeing patients from lifetime therapy.

Bepirovirsen was initially developed by Ionis Pharmaceuticals, an RNA-targeted therapeutics company, and in 2019, GSK advanced $25 million to partner with Ionis Pharmaceuticals for subsequent development.

This clinical trial was specifically designed to assess the safety and efficacy of bepirovirsen treatment in patients with hepatitis B who were getting standard treatment with nucleoside analogs and in patients with hepatitis B who were not receiving standard treatment with nucleoside analogs.

• For hepatitis B patients treated with nucleoside analogs (227), 300 mg of bepirovirsen per week for 24 weeks, 28% of whom achieved undetectable levels of both HBsAg and hepatitis B virus DNA at the end of treatment.
• For patients with hepatitis B not treated with nucleoside analogues (230), treated with 300 mg of bepirovirsen weekly for 24 weeks, 29% of whom achieved undetectable levels of both HBsAg and hepatitis B virus DNA at the end of treatment.

The persistence of these treatment effects is still a work in progress.

GSK is also looking at using bepirovirsen in conjunction with other therapies including pegylated interferon and targeted immunotherapy to help the remaining 70% of hepatitis B patients achieve a functional cure.

Overall, the preliminary outcomes from this Phase 2b clinical trial, combined with earlier clinical results, justify GSK's decision to initiate a Phase 3 clinical program for bepirovirsen in hepatitis B.

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