Evolving Concepts: Metabolic Dysfunction-Associated Steatohepatitis (MASH) Clinical Program Design

By Peyton Sandroni, PhD, Fellow, Clinical Research Methodology; MarieElena Cordisco, MA, NP-C, APRN, Senior Director, Therapeutic Strategy Lead, Cardiovascular & Metabolic; Michael Murphy, MD PhD, Chief Medical and Scientific Officer; and Alessandra Vignola, President, Cardiovascular & Metabolic

The shift from non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) to the newly adopted terms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) represents a significant evolution in the understanding of hepatic conditions associated with metabolic disorders. This updated terminology reflects a growing consensus among global therapeutic experts to better describe the spectrum of liver diseases linked to various metabolic dysfunctions.

As the field progresses, clinical trials for MASH are advancing rapidly, with a diverse range of enrollment strategies and treatment approaches emerging. Regulatory bodies such as the FDA and EMA are also adapting, providing updated guidance on patient populations, study designs, and clinical endpoints.

Recent FDA approvals and ongoing Phase 3 trials for drugs like resmetirom and pegozafermin highlight the strides being made in MASH therapeutic development. This discussion explores the evolving landscape of MASH, including key trial considerations and factors influencing the development of new treatments.