MASH Pipeline Developments and Emerging Therapies to Watch in 2026, With Mazen Noureddin, MD, MHSc

After years of setbacks and uncertainty, the therapeutic landscape for metabolic dysfunction–associated steatohepatitis (MASH) and metabolic dysfunction–associated steatotic liver disease (MASLD) has entered a decisive new phase. Once characterized by failed trials and a lack of approved therapies, the field has rapidly shifted toward cautious optimism, driven by regulatory clarity, advancing endpoints, and a deepening late-stage pipeline.

“It’s an exciting landscape,” Mazen Noureddin, MD, MHSc, professor of medicine at Houston Methodist Hospital and co-chairman of the Board for Summit and Pinnacle Clinical Research, told HCPLive. “There used to be a pessimistic look on the field from patients and investors. Not so much from researchers, because we started seeing the light at the end of the tunnel and the difficult end points started being formalized back then, and now, in 2026 we're starting with 2 drugs approved, resmetirom and semaglutide.”

He describes 2026 as a pivotal “year of action” for MASH drug development, with 2027 poised to deliver critical outcomes. He notes that the field has already crossed an important threshold, with resmetirom and semaglutide receiving accelerated approvals, while confirmatory outcomes trials continue. Now, the focus is now on demonstrating long-term benefit, particularly the prevention of cirrhosis and hepatic decompensation.

Noureddin additionally highlights several late-stage programs that he believes will shape the next era of care, including the ongoing MAESTRO outcomes trial of resmetirom in patients with cirrhosis. He also points to the momentum around FGF21-based therapies, including efruxifermin, pegozafermin, and efimosfermin, noting multiple high-impact phase 2 publications and active phase 3 programs following major acquisitions by large pharmaceutical companies.

Beyond these programs, Noureddin underscores growing enthusiasm for dual- and triple-agonist approaches, including GLP-1/glucagon combinations now in phase 3 development. He also draws attention to emerging innovation earlier in the pipeline, such as gene therapy approaches targeting FGF21 and novel agents expected to deliver biopsy data in 2026.

Despite this progress, Noureddin also calls attention to persistent unmet needs, including effective therapies for patients with cirrhosis.

“That is doable, but we don't have it handy for the patients, and the clock is ticking in terms of [getting it to them] before they decompensate,” he said. “I would like to see a drug approved as soon as possible for this patient population in particular.”

He also references the development of combination treatment regimens and the urgent push to move away from liver biopsy as a trial requirement as unmet needs he wants to see addressed, but expresses optimism around recent progress in the development of treatments for metabolic dysfunction and alcohol-associated liver disease (MetALD).

Looking ahead, Noureddin says he believes the next 5 years will define the backbone of MASH treatment algorithms, even as progress in decompensated cirrhosis may take longer. Still, he characterizes the current moment as unprecedented and marked by momentum, collaboration, and hope for patients who have long lacked therapeutic options.

Editors’ note: Noureddin reports relevant disclosures with Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Takeda, 89BIO, Altimmune, Boehringer Ingelheim, and others.

References:

1. Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed January 28, 2026. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash

2. Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. HCPLive. August 15, 2025. Accessed January 28, 2026. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash

3. Brooks A. Efruxifermin Shows Potential for Fibrosis Reduction in Phase 2b MASH Cirrhosis Trial. HCPLive. May 9, 2025. Accessed January 28, 2026. https://www.hcplive.com/view/exfruxifermin-misses-primary-endpoint-phase-2b-compensated-mash-cirrhosis-trial

4. Brooks A. Pegozafermin Enters Phase 3 Clinical Trial Program for MASH, Fibrosis. HCPLive. March 12, 2024. Accessed January 28, 2026. https://www.hcplive.com/view/pegozafermin-enters-phase-3-clinical-trial-program-mash-fibrosis

5. Noureddin M. Once-Monthly Efimosfermin Alfa Shows Promise for MASH in Phase 2 Study. HCPLive. May 5, 2025. Accessed January 28, 2026. https://www.hcplive.com/view/once-monthly-efimosfermin-alfa-shows-promise-mash-in-phase-2-study