The EASL 2024 meeting offered a great opportunity for hepatologists from around the world to discuss the latest data and tackle challenges in liver disease. Metabolic dysfunction-associated steatohepatitis (MASH) was a hot topic, with several exciting studies making waves. This article highlights some of the most interesting and promising research on MASH presented at the meeting, showing the progress being made in understanding and treating this complex liver condition.
Efruxifermin shows sustained efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH)
Late-breaking data from the phase IIb HARMONY study highlighted the efficacy and safety of efruxifermin in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stages 2 or 3 (F2–F3).Â
The study met its initial primary endpoint at 24 weeks, with 41% of patients receiving 50 mg and 39% receiving 28 mg of efruxifermin achieving at least a one-stage improvement in fibrosis, compared to 20% in the placebo group. By week 96, these response rates increased to 75% for the 50 mg dose and 46% for the 28 mg dose, compared to 24% for placebo. Additionally, 36% of patients on the 50 mg dose and 31% on the 28 mg dose achieved a two-stage improvement in fibrosis without worsening MASH, surpassing the 3% improvement seen in the placebo group.
Efruxifermin was generally well tolerated throughout the study, with no reports of liver injury or decompensation events. The most common adverse events were mild to moderate gastrointestinal issues, consistent with those observed during the initial 24 weeks.
These results underscore efruxifermin’s sustained efficacy and safety in improving fibrosis for patients with MASH, marking it as a promising treatment option for this challenging condition.Â
Survodutide shows promising results in phase II trials for MASH and liver fibrosis
Promising data from a phase II trial demonstrates the efficacy and safety of survodutide in treating MASH and liver fibrosis. In the multinational, double-blind trial, 295 adult patients with biopsy-confirmed MASH and liver fibrosis (stages F2-F3) were randomly assigned to weekly doses of survodutide (2.4 mg, 4.8 mg or 6 mg) or placebo. The primary endpoint, (≥2 point decrease in NAS with ≥1 point decrease in lobular inflammation or ballooning sub-scores) without worsening of fibrosis after 48 weeks, was achieved by 64.3% to 83% of survodutide-treated patients with a dose of 2.4 mg and 4.8 mg respectively, compared to 18.2% in the placebo group.
Fifty percent of patients on 6 mg survodutide improved by at least one fibrosis stage versus 21.2% on placebo. Survodutide significantly reduced the Non-alcoholic Fatty Liver Disease Activity Score (NAS) by 2.8 to 3.3 points, compared to 0.4 with placebo. Improvements in ALT and AST levels were significantly greater in the survodutide groups. Adverse events were similar across groups, with gastrointestinal disorders being more common in survodutide-treated patients (84.9–87.8% versus. 56.8% with placebo).
These results suggest that survodutide may offer a promising new treatment option for patients with MASH and advanced liver fibrosis, potentially reducing the progression to cirrhosis and the need for liver transplants.
Denifanstat shows encouraging results in FASCINATE-2 trial, paving way for phase III
The FASCINATE-2 phase IIb trial demonstrated that denifanstat, a fatty acid synthase inhibitor, significantly outperformed placebo in treating metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis stages 2 and 3.
At 52 weeks included 36% of patients on denifanstat achieved MASH resolution without worsening fibrosis compared to 13% on placebo and 41% of patients on denifanstat showed at least a one-stage improvement in fibrosis without worsening MASH compared to 18% on placebo.
The trial enrolled 168 patients who were randomized to receive either denifanstat or placebo. Both the intention-to-treat (ITT) and modified intention-to-treat (mITT) populations showed significant improvements in liver histology and fibrosis reduction. Additionally, denifanstat led to substantial improvements in the nonalcoholic fatty liver disease score (NAS) and reduced progression to stage 4 cirrhosis. Adverse events were mostly mild to moderate, with hair thinning being reversible. These promising results support further clinical development of denifanstat in phase III trials for MASH.
Weight-based dosing of resmetirom shows enhanced efficacy in heavier MASH patients in MAESTRO-NASH trial
Patients with metabolic dysfunction-associated steatohepatitis (MASH) who weigh more than 100 kg or have a BMI over 35 kg/m² showed slightly better responses to a 100 mg dose of resmetirom compared to an 80 mg dose. This was observed in the phase III MAESTRO-NASH trial, which supports the weight-based dosing recommendations for resmetirom. The study involved 966 adults with biopsy-proven MASH and evaluated the efficacy and safety of 80 mg and 100 mg doses. Results showed that higher doses led to improved NASH resolution and fibrosis reduction, especially in patients with higher weight or BMI. Resmetirom was well tolerated, although higher doses resulted in slightly more gastrointestinal-related discontinuations. The findings reinforce the dosing guidelines and suggest durable benefits over three years of treatment.
Metabolic surgery slashes liver complications in MASH patients in results from the SPECCIAL study
Findings from the SPECCIAL study showed metabolic surgery significantly reduces major adverse liver outcomes and progression to decompensation in patients with metabolic dysfunction-associated steatohepatitis (MASH) and compensated cirrhosis. Over 15 years of follow-up, surgery reduced major adverse liver outcomes by 72% and progression to decompensation by 80%. The observational study assessed 36,912 liver biopsies and compared 62 patients who underwent metabolic surgery with 106 nonsurgical controls. Results showed the cumulative incidence of major adverse liver outcomes was 20% in the surgical group versus 46% in the nonsurgical group. Similarly, the incidence of progression to decompensation was 15% versus 30%, respectively. Metabolic surgery was also found to be safe, with no treatment-related deaths reported.
Disclosures:Â This article was created by the touchIMMUNOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
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