AHB-137: An Investigational Antisense Oligonucleotide for Chronic Hepatitis B

I. Introduction to AHB-137 and Chronic Hepatitis B

Chronic hepatitis B (CHB) infection, caused by the hepatitis B virus (HBV), represents a significant global health challenge, affecting an estimated 290 million individuals worldwide.[1] The long-term persistence of HBV can lead to severe liver complications, including cirrhosis and hepatocellular carcinoma, contributing to substantial morbidity and mortality.[1] Current therapeutic strategies for CHB primarily involve nucleos(t)ide analogues (NAs) and pegylated interferon-alpha (pegIFN-α).[4] While NAs effectively suppress HBV DNA replication, and pegIFN-α can offer a finite treatment course, neither reliably leads to a "functional cure".[5] A functional cure is typically defined as sustained loss of hepatitis B surface antigen (HBsAg) and undetectable serum HBV DNA for at least 24 weeks after completing a finite course of therapy, with or without seroconversion to anti-HBs antibodies.[5] Achieving such a cure is rare with existing treatments, with HBsAg loss rates being notably low.[5] This unmet medical need drives the development of novel therapeutic agents.

AHB-137 is an investigational drug developed by AusperBio Therapeutics Inc. and Ausper Biopharma Co., Ltd. (collectively AusperBio).[1] It is an unconjugated antisense oligonucleotide (ASO) specifically designed to target HBV infection with the goal of achieving a functional cure.[8] AHB-137 emerged from AusperBio's proprietary Med-Oligo™ ASO technology platform, which aims to enhance the therapeutic properties of ASOs.[8] This report provides a comprehensive overview of AHB-137, including its mechanism of action, preclinical findings, extensive clinical development program, regulatory status, and an expert analysis of its potential role in the evolving CHB treatment landscape.

II. The Challenge of Functional Cure in Chronic Hepatitis B