The Future of MASH Care: New Agents in Clinical Development

On March 14, 2024, the US Food and Drug Administration (FDA) made history when it granted accelerated approval to Madrigal Pharmaceuticals’ resmetirom (Rezdiffra), making it the first and only treatment for noncirrhotic nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH).

One year later, resmetirom’s impact on clinical practice and patient care continues to evolve. In recognition of the anniversary of the landmark decision, the latest HCPLive RX Review spotlights a conversation between a trio of subject matter experts reflecting on the past year of having resmetirom as a treatment option for patients, remaining unmet needs in MASH management, and the evolving therapeutic pipeline poised to further transform care.

Estimated to affect more than 30% of the global population, MASLD is the most common chronic liver disease around the world. MASH represents an advanced stage of MASLD and has historically lacked treatment options beyond lifestyle changes with diet and exercise. In the absence of pharmacologic therapies, weight loss served as the cornerstone of disease management.

This changed in March 2024, when resmetirom became the first and only FDA-approved MASH therapeutic, earning accelerated approval for the treatment of noncirrhotic MASH with moderate to advanced fibrosis. Although lifestyle interventions continue to play a pivotal role in MASH care, as the thyroid hormone receptor-beta selective agonist is indicated in conjunction with diet and exercise, they are no longer the only tools available for disease management.

In the third segment of our 6-part HCPLive RX Review on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre asks Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about promising investigational therapies in the pipeline and how they might compare to resmetirom.

Noureddin begins the conversation by emphasizing combination therapy rather than competition, likening MASH treatment to type 2 diabetes management—where medications can be added, adjusted, or switched over time.

Looking at the MASH pipeline, he highlights semaglutide’s 72-week data, recent phase 2 data for efruxifermin, and the potential of dual-agents like GLP-1/GIP receptor agonists. Overall, Noureddin expresses optimism that the field is on the cusp of additional significant therapeutic advancements.

Arab echoes Noureddin’s optimism and stressed the importance of combination therapy—not just within GLP-1 receptor agonists, but also pairing them with FGF21 analogs, PPAR agonists, or other therapeutic classes.

Moderator:

Jeff McIntyre is the vice president of Liver Health Programs at the Global Liver Institute.

Panelists:

Mazen Noureddin, MD, MHSc, is a professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute.

Juan Pablo Arab, MD, is an associate professor of medicine in the division of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University School of Medicine

Noureddin has relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Takeda, Terns, and others. Arab and McIntyre have no relevant disclosures.

References:

1. US Food and Drug Administration. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. March 14, 2024. Accessed March 13, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease

2. Brooks, A. Stephen Harrison, MD: Promising Phase 3 Data for Resmetirom in NASH, Fibrosis. HCPLive. February 7, 2024. Accessed March 13, 2025. https://www.hcplive.com/view/stephen-harrison-md-promising-phase-3-data-resmetirom-nash-fibrosis.