Emerging Treatments for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

Area of Science:

• Hepatology and Gastroenterology
• Clinical Pharmacology
• Drug Development

Background:

• Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with limited treatment options.
• Histologic improvement is a key endpoint in evaluating NASH therapies.
• Phase II clinical trials provide crucial data on drug efficacy and safety.

Purpose of the Study:

• To review completed phase II randomized clinical trials for NASH.
• To analyze compounds demonstrating histologic effects in NASH patients.
• To discuss preliminary data and failed therapeutic approaches.

Main Methods:

• Systematic review of high-quality published phase II randomized clinical trials.
• Inclusion of studies on obeticholic acid, elafibranor, liraglutide, cenicriviroc, and selonsertib.
• Analysis of compounds that did not meet primary endpoints, including cysteamine bitartrate and long-chain polyunsaturated fatty acids.

Main Results:

• Obeticholic acid, elafibranor, and liraglutide showed effects on NASH histology in phase II trials.
• Preliminary data for cenicriviroc and selonsertib were reviewed.
• Cysteamine bitartrate and long-chain polyunsaturated fatty acids did not achieve histologic improvement endpoints.

Conclusions:

• Several compounds show promise for NASH treatment, warranting further investigation in phase III trials.
• Understanding treatment failures is critical for optimizing future drug development strategies.
• This review synthesizes key phase II findings to inform the NASH therapeutic landscape.