Hepatology First Half Recap: 2025

The first half of 2025 brought notable momentum across hepatology, with advancements spanning autoimmune liver disease, pediatric and genetic cholestasis, viral hepatitis, and metabolic dysfunction–associated steatohepatitis (MASH). Regulatory milestones included a phase 3 pathway for nebokitug in primary sclerosing cholangitis (PSC), label and formulation approvals for maralixibat and glecaprevir/pibrentasvir, and promising data for zetomipzomib in autoimmune hepatitis.

MASH remained a central focus, with major phase 2 and 3 data readouts for semaglutide, efruxifermin, and pemvidutide reinforcing the field’s momentum one year after the landmark FDA approval of resmetirom. As emerging therapies continue to show promise for both steatohepatitis resolution and fibrosis reduction, 2025 is shaping up as a pivotal year in the evolution of liver care.

Here’s a recap of what made headlines in the first half of 2025:

Nebokitug (CM-101) Gets FDA Runway for PSC Approval

On February 19, 2025, Chemomab Therapeutics announced the successful completion of an end-of-phase 2 meeting with the FDA as well as alignment with the agency on the design of a single phase 3 registration study for nebokitug (CM-101) for the treatment of PSC.

“Until now, the pathway to drug approval in PSC has been problematic due to the lack of validated surrogate endpoints and clarity around primary efficacy endpoints for PSC registration trials. This has been a major hindrance to the development of effective therapies for PSC,” Christopher Bowlus, MD, the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine, commented. “The agreed composite endpoint approach for the nebokitug trial enhances our chances of efficiently and accurately identifying the potential clinical benefits of this promising new drug.”

FDA Approves Maralixibat (Livmarli) Tablet for Alagille Syndrome, PFIC

On April 14, 2025, the FDA approved a new tablet formulation of maralixibat (Livmarli) for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC). In addition to its already approved indications in ALGS and PFIC, maralixibat is being evaluated in the phase 3 EXPAND study in other settings of cholestatic pruritus.

FDA Approves Glecaprevir/Pibrentasvir (Mavyret) Label Expansion for Acute HCV

On June 11, 2025, the FDA approved a label expansion for glecaprevir/pibrentasvir (Mavyret), an oral pangenotypic direct acting antiviral (DAA) therapy. With the decision, glecaprevir/pibrentasvir became approved for the treatment of adults and pediatric patients ≥ 3 years of age with acute or chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

Zetomipzomib Shows Promise for Autoimmune Hepatitis in Phase 2a PORTOLA Trial

According to a March 25, 2025, press release from Kezar Life Sciences, positive topline results from the PORTOLA phase 2a clinical trial in patients with autoimmune hepatitis showed treatment with zetomipzomib resulted in steroid-sparing biochemical remissions in accordance with AASLD treatment guidelines.

“I am impressed by the totality of efficacy and safety data from the PORTOLA study,” said Gideon Hirschfield, Chair of Autoimmune Liver Disease Research and Director of the Francis Family Liver Clinic, at the Toronto General Hospital. “Zetomipzomib represents a potent and targeted therapy for patients, and I believe these results will positively contribute to the design of a registrational trial of zetomipzomib in AIH, where patients are in need of better treatment options.”

Semaglutide Improves Steatohepatitis, Fibrosis in Phase 3 MASH Trial

Results from part 1 of the phase 3 Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis (ESSENCE) trial shed light on the safety and efficacy of semaglutide for the treatment of patients with metabolic dysfunction–associated steatohepatitis (MASH) and stage 2/3 fibrosis. Data published in The New England Journal of Medicine show once-weekly semaglutide 2.4 mg outperformed placebo for resolution of steatohepatitis without worsening of fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.

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

Although 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, the 50 mg dose showed 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 pemvidutide in patients with MASH were announced on June 26, 2025, and showed the trial met its primary endpoint for statistically significant MASH resolution without worsening of fibrosis, which occurred 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. Additionally, weight loss of up to 6.2% was observed at 24 weeks with no plateauing.

Celebrating 1 Year of Resmetirom, Progress in MASH/MASLD

Despite all of the pipeline activity around MASH, resmetirom (Rezdiffra) remains the only FDA-approved treatment option. March 14, 2025, marked the 1-year anniversary of the thyroid hormone receptor-beta selective agonist’s accelerated FDA approval for the treatment of noncirrhotic MASH with moderate to advanced fibrosis.

In recognition of the anniversary of the landmark decision and resmetirom’s evolving impact on clinical practice and patient care, this 6-part HCPLive RX Review featured insight from a trio of subject matter experts.