Unmet Needs in MASH Care

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 second 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 unmet needs in MASH care that have not been addressed by the availability of resmetirom.

Noureddin highlights the need for improved screening, particularly streamlining multi-step processes and expanding the availability of blood-based tests to complement transient elastography. He underscores the importance of integrating MASLD and MASH screening into primary care as a quality metric, akin to established protocols for diabetic retinopathy and nephropathy.

“The more we know, the more we realize that there's many more things that we don't know,” Arab added.

Specifically, he calls attention to the importance of personalized care by identifying which patients respond best to specific treatments and exploring combination therapies. He notes that while resmetirom targets the liver, MASLD often coexists with other comorbidities, necessitating a broader treatment strategy. Screening remains a critical hurdle, as current efforts only reach a small fraction of affected individuals. Arab further raises questions about the role of alcohol in the broader steatotic liver disease spectrum, particularly in MetALD patients, and how emerging therapies might be utilized in these populations.

Despite these challenges, Arab expresses optimism, citing increased awareness and promising therapeutic developments as signs of meaningful progress in the field.

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.