Lam R, Lim JK. Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents. World J Hepatol 2024; 16(3): 331-343 [PMID: 38577537 DOI: 10.4254/wjh.v16.i3.331]
Corresponding Author of This Article
Joseph K Lim, MD, Professor, Section of Digestive Diseases, Yale University School of Medicine, Yale Liver Center, 333 Cedar Street, LMP 1080, New Haven, CT 06520, United States. joseph.lim@yale.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Mar 27, 2024; 16(3): 331-343 Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.331
Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents
Robert Lam, Joseph K Lim
Robert Lam, Joseph K Lim, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, United States
Author contributions: Lam R collected the data; Lam R and Lim JK wrote and revised the manuscript.
Conflict-of-interest statement: Robert Lam reports no conflict of interest; Joseph K Lim has received research funding (to Yale University) from Gilead, Intercept, Inventiva, Novo Nordisk, Pfizer, and Viking.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph K Lim, MD, Professor, Section of Digestive Diseases, Yale University School of Medicine, Yale Liver Center, 333 Cedar Street, LMP 1080, New Haven, CT 06520, United States. joseph.lim@yale.edu
Received: November 27, 2023 Peer-review started: November 27, 2023 First decision: January 5, 2024 Revised: January 23, 2024 Accepted: February 29, 2024 Article in press: February 29, 2024 Published online: March 27, 2024
Abstract
Chronic hepatitis B virus (HBV) infection affects over 295 million people globally and an estimated 1.6 million people in the United States. It is associated with significant morbidity and mortality due to cirrhosis, liver failure, and liver cancer. Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression, which in turn has been associated with a decreased risk of liver complications. However, current antiviral regimens are limited by concerns with adverse effects, adherence, resistance, long-term treatment, and ongoing risk for liver events. Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen (HBsAg) loss and suppression of HBV DNA. Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B, including core/capsid inhibitors, entry inhibitors, RNA interference (siRNA/ASO), HBsAg inhibitors, Toll-like receptor agonists, checkpoint inhibitors, and therapeutic vaccines.
Core Tip: Novel investigational agents targeting functional cure [sustained hepatitis B surface antigen (HBsAg) loss and undetectable hepatitis B virus (HBV) DNA] are currently in clinical trial development. Herein we review key evidence from phases 2 and 3 trials defining the efficacy and safety profiles for key investigational agents, including core/capsid inhibitors, entry inhibitors, RNA interference (siRNA/ASO), HBsAg inhibitors, Toll-like receptor agonists, checkpoint inhibitors, and therapeutic vaccines.
