GSK's Antisense Oligonucleotide Drug GSK3228836 Receives Chinese Regulatory Approval for Clinical Trials in Chronic Hepatitis B

Source: PharmaCube Info

Author: Sunshine

On August 12, the official website of the Center for Drug Evaluation (CDE) indicated that the clinical trial application for GlaxoSmithKline’s antisense oligonucleotide drug GSK3228836 injection has been approved by the National Medical Products Administration (NMPA) for the treatment of chronic hepatitis B. Previously, on August 9, GSK3228836 injection had already been granted a proposed breakthrough therapy designation by the CDE.

Source: PharmaGo

Chronic hepatitis B is a chronic disease characterized by persistent infection with the hepatitis B virus (HBV) for more than 6 months, leading to varying degrees of hepatic inflammation, necrosis, and/or fibrosis. Globally, approximately 260 million individuals are living with hepatitis B. Each year, HBV-related liver failure and liver cancer result in an estimated 900,000 deaths, making it one of the major global public health burdens. In China, HBV infection accounts for 77% and 84% of liver cirrhosis and hepatocellular carcinoma (HCC) cases, respectively.

Current nucleoside and nucleotide analogue drugs used for the treatment of hepatitis B can suppress the hepatitis B virus but cannot completely eradicate it from the body. This is because after entering the host, the hepatitis B virus integrates its genome into the host hepatocyte nuclear DNA to form covalently closed circular DNA (cccDNA), and subsequently utilizes the host cellular machinery to synthesize mRNA and the proteins required for viral particle assembly. Consequently, the relapse rate of chronic hepatitis B remains high following treatment discontinuation.

GSK3228836 is an antisense oligonucleotide that specifically recognizes the mRNA responsible for expressing viral antigens (pathogenic proteins) in HBV-infected hepatocytes. By mobilizing the liver's endogenous enzymatic machinery to inactivate the viral mRNA, it suppresses HBsAg levels, aiming to achieve a functional cure for hepatitis B. A functional cure refers to the loss of HBsAg following a finite course of treatment, with or without seroconversion, undetectable serum HBV DNA, alleviation of hepatic inflammation and fibrosis, and a progressively reduced risk of developing hepatocellular carcinoma (HCC) over time.