MASH: A New Dual-Action Therapy for Liver Disease & Metabolic Dysfunction
The global rise in obesity is dramatically reshaping the landscape of liver transplantation, with metabolic dysfunction-associated steatotic liver disease (MASLD) rapidly becoming a leading cause for the procedure. This trend presents a complex challenge for both donor and recipient selection, surgical outcomes and long-term graft survival, according to research published in October 2025.
MASLD, formerly known as nonalcoholic steatohepatitis (NASH), is estimated to affect 22 million people in the United States. More than 80 percent of patients with MASLD are also considered overweight or obese. The increasing prevalence of obesity is predicted to make MASH the leading indication for liver transplantation in the U.S. Within the next decade, according to a study published in MDPI.
Current treatments for MASLD typically target either the metabolic or liver-specific causes of the disease, often failing to address the totality of the condition. Altimmune, a biopharmaceutical company, is developing a product candidate, pemvidutide, designed to address both the metabolic and liver-related aspects of MASLD. Pemvidutide is a glucagon/GLP-1 dual receptor agonist, with a one-to-one ratio of these two activities, and incorporates a proprietary structure called EuPort, intended to allow for weekly dosing and potentially improve tolerability.
Glucagon, a component of pemvidutide, is designed to drive liver-directed effects, reducing liver fat, inflammation, and fibrosis. The GLP-1 receptor agonist component addresses metabolic dysfunction through appetite suppression and weight loss, and may also contribute to anti-inflammatory activity. Altimmune believes the combination of these mechanisms could function as a synergistic, combination therapy.
Data from Altimmune’s Phase 2b IMPACT trial of pemvidutide showed early MASH resolution, anti-inflammatory, and antifibrotic activity, alongside weight loss and other metabolic improvements. Importantly, the trial also indicated a favorable tolerability profile, with lower discontinuation rates due to adverse events compared to placebo. The Food and Drug Administration recently granted pemvidutide Breakthrough Therapy Designation, recognizing its potential to offer improvement over existing therapies.
Altimmune plans to initiate a Phase 3 MASH program in 2026, aiming to demonstrate early reductions in liver fat and inflammation, clinically relevant fibrosis improvements, quality weight loss that preserves lean muscle mass, and a favorable tolerability profile. The company is also exploring pemvidutide’s potential for treating alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), conditions that share overlapping pathophysiology with MASLD.
Preclinical research suggests pemvidutide may rapidly decrease drinking behavior, and ongoing Phase 2 trials are evaluating its efficacy in AUD and ALD. The company believes the benefits of glucagon acting directly on the liver may help improve hepatic damage resulting from sustained alcohol use. Altimmune is strengthening its organizational foundation, including securing capital and talent, to advance pemvidutide through late-stage clinical development.