2025 marked a pivotal year for metabolic dysfunction-associated steatohepatitis (MASH) and the broader metabolic dysfunction-associated steatotic liver disease (MASLD) landscape, as the field moved decisively from first approvals toward therapeutic expansion and regulatory maturation. Momentum built on the foundation laid in 2024, with new data, evolving guidance, and growing confidence in noninvasive endpoints reshaping both drug development and clinical practice.

Resmetirom remained central to the year’s narrative as it reached the 1-year anniversary of its US Food and Drug Administration (FDA) approval and delivered compelling new data in compensated MASH cirrhosis, including marked reductions in liver stiffness. The FDA’s acceptance of FibroScan liver stiffness measurement as a reasonably likely surrogate endpoint further underscored a turning point for the field, signaling a pathway toward faster, more feasible clinical trials and broader therapeutic innovation.

At the same time, the MASH pipeline continued to diversify. Pemvidutide emerged as a standout with early histologic efficacy, meaningful weight loss, and sustained antifibrotic signals as it advanced toward phase 3 development, while efruxifermin offered longer-term hints of fibrosis benefit despite mixed primary results. The FDA approval of semaglutide for noncirrhotic MASH and subsequent American Association for the Study of Liver Diseases (AASLD) guidance updates reinforced the expanding role of metabolic therapies, collectively defining 2025 as a year of consolidation, acceleration, and clearer direction for MASH and MASLD care.

FDA News

FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH

On August 15, 2025, the FDA approved Novo Nordisk’s semaglutide (Wegovy) injection 2.4 mg for the treatment of adults with MASH with moderate to advanced fibrosis, but not with cirrhosis, in conjunction with a reduced calorie diet and increased physical activity. The decision made semaglutide the second-ever FDA-approved MASH therapeutic and was based on results from the phase 3 ESSENCE trial investigating the effects of once-weekly semaglutide 2.4 mg injection on liver histology in adults with MASH and moderate to advanced liver fibrosis at week 72.

FDA Accepts FibroScan Letter of Intent for Surrogate Endpoint in MASH Trials

On September 8, 2025, the FDA’s Center for Drug Evaluation and Research, Office of New Drugs accepted Echosens’ Letter of Intent for the qualification of Liver Stiffness Measurement (LSM) by VCTE (FibroScan) as a reasonably likely surrogate endpoint in clinical trials for MASH. The decision marked the first time the FDA accepted the initiation of the qualification process of a noninvasive test as a reasonably likely surrogate endpoint in drug development for MASH. The Letter of Intent included official letters of support from Eli Lilly, Boehringer Ingelheim, and Novo Nordisk.

Trial Updates and New Guidelines

Resmetirom Reduces Liver Stiffness in Compensated MASH Cirrhosis

Positive 2-year results from the open-label compensated MASH cirrhosis (F4c) arm of the phase 3 MAESTRO-NAFLD-1 trial of Madrigal Pharmaceuticals’ resmetirom (Rezdiffra) show patients treated with resmetirom achieved marked reductions in liver stiffness, a surrogate for fibrosis, as measured by VCTE. The data represent the largest reduction in liver stiffness reported to date in an F4c MASH population.

Efruxifermin Shows Potential for Fibrosis Reduction in Phase 2b MASH Cirrhosis Trial

Efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue being developed for the treatment of MASH, failed to significantly reduce fibrosis without worsening of MASH at 36 weeks in a phase 2b trial. Despite missing the trial’s primary endpoint, the 50 mg dose of efruxifermin may have possible benefit on fibrosis reduction at 96 weeks. Notably, efruxifermin also appeared to be associated with improvements in MASH-related histologic findings, noninvasive markers of liver injury and fibrosis, and markers of glucose and lipid metabolism.

Pemvidutide Shows Significant MASH Effects, Weight Loss at 24 Weeks in Phase 2b IMPACT Trial

Positive topline results from the phase 2b IMPACT trial of Altimmune’s pemvidutide in patients with MASH show the trial met its primary endpoint, with statistically significant MASH resolution without worsening of fibrosis in up to 59.1% of participants and fibrosis improvement without worsening of MASH in up to 34.5% of participants in intent-to-treat analyses as well as weight loss of up to 6.2% at 24 weeks with no plateauing. The data made pemvidutide the first product candidate to demonstrate significant MASH effects and weight loss at 24 weeks.

AASLD Releases Updated Practice Guidance on Semaglutide (Wegovy) for MASH

In accordance with the addition of semaglutide to the MASH treatment landscape, the AASLD released an updated practice guidance on use of this therapy for MASH. The document serves as an update to the 2023 AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease (NAFLD), now known as MASLD, and includes guidance on patient selection, safety considerations, treatment response, and concomitant therapy.

Pemvidutide Shows Continued Antifibrotic Activity for MASH, Progresses to Phase 3 Trial

Topline 48-week data from the phase 2b IMPACT trial of pemvidutide, a balanced 1:1 glucagon/GLP-1 dual receptor agonist, in patients with MASH showed treatment with pemvidutide achieved statistically significant improvements across treatment arms in key noninvasive tests, including ELF and LSM, versus placebo. Of note, these data exhibited continued reductions from week 24 and provide evidence of continued improvement in antifibrotic activity with both treatment doses.

Parent company Altimmune additionally announced that it held a productive End-of-Phase 2 meeting with the FDA resulting in alignment on the parameters for a registrational phase 3 trial of pemvidutide for MASH patients with moderate to advanced liver fibrosis.

Feature Content/Podcasts

Celebrating 1 Year of Resmetirom, Progress in MASH/MASLD

In honor of the 1 year anniversary of resmetirom’s FDA approval, a trio of expert hepatologists examined updates and unmet needs in the management of MASH and MASLD, highlighting resmetirom’s impact on disease management and looking ahead to what might be next in the pipeline.

Liver Lineup: GLP-1 RAs and FGF21s for MASH, with Mary Rinella, MD

In this episode of Liver Lineup: Updates and Unfiltered Insights, hosts Nancy Reau, MD, and Kimberly Brown, MD, sit down with Mary (Maru) Rinella, MD, to discuss the rapidly evolving therapeutic landscape for MASH, with a particular focus on GLP-1s and FGF21s in development.

References

1. Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. HCPLive. August 15, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash

2. Brooks A. FDA Accepts FibroScan Letter of Intent for Surrogate Endpoint in MASH Trials. HCPLive. September 9, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/fda-accepts-fibroscan-letter-of-intent-for-surrogate-endpoint-in-mash-trials

3. Brooks A. Resmetirom Reduces Liver Stiffness in Compensated MASH Cirrhosis. HCPLive. February 26, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/resmetirom-reduces-liver-stiffness-compensated-mash-cirrhosis

4. Brooks A. Efruxifermin Shows Potential for Fibrosis Reduction in Phase 2b MASH Cirrhosis Trial. HCPLive. May 9, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/exfruxifermin-misses-primary-endpoint-phase-2b-compensated-mash-cirrhosis-trial

5. Brooks A. Pemvidutide Shows Significant MASH Effects, Weight Loss at 24 Weeks in Phase 2b IMPACT Trial. HCPLive. June 26, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/pemvidutide-shows-significant-mash-effects-weight-loss-24-weeks-phase-2b-impact-trial

6. Brooks A. AASLD Releases Updated Practice Guidance on Semaglutide (Wegovy) for MASH. HCPLive. November 7, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/aasld-releases-updated-practice-guidance-semaglutide-wegovy-mash

7. Brooks A. Pemvidutide Shows Continued Antifibrotic Activity for MASH, Progresses to Phase 3 Trial. HCPLive. December 19, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/pemvidutide-shows-continued-antifibrotic-activity-mash-progresses-to-phase-3-trial

8. Celebrating 1 Year of Resmetirom, Progress in MASH/MASLD. HCPLive. March 14, 2025. Accessed December 22, 2025. https://www.hcplive.com/special-report/celebrating-1-year-of-resmetirom-progress-in-mash-masld

9. Reau N, Brown KA, Rinella M. Liver Lineup: GLP-1 RAs and FGF21s for MASH, with Mary Rinella, MD. HCPLive. August 20, 2025. Accessed December 22, 2025. https://www.hcplive.com/view/liver-lineup-glp-1-ras-and-fgf21s-for-mash-with-mary-rinella-md