Lilly's Tirzepatide Superior to Placebo for MASH Resolution, With Over 50% Patients Showing Fibrosis Improvement at 52 Weeks

Eli Lilly and Company revealed detailed findings from the SYNERGY-NASH phase 2 clinical trial at the European Association for the Study of the Liver (EASL) Congress 2024, with simultaneous publication in The New England Journal of Medicine. This study investigated the use of tirzepatide in adult patients diagnosed with metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or 3 fibrosis. The trial included 190 participants, with or without type 2 diabetes, who were administered varying doses of tirzepatide or a placebo over a 52-week period.

The primary endpoint of the study was MASH resolution without worsening fibrosis, which was achieved in 51.8%, 62.8%, and 73.3% of participants taking 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively. This is compared to only 13.2% in the placebo group. Secondary endpoints highlighted that 59.1%, 53.3%, and 54.2% of participants on the respective doses of tirzepatide experienced a one-stage or greater improvement in fibrosis without worsening MASH, compared to 32.8% in the placebo group.

The study also assessed additional secondary endpoints, where tirzepatide showed improvements in body weight, liver injury blood markers, and biomarkers related to liver fat, inflammation, and fibrosis. Although the phase 2 study was not designed to definitively prove tirzepatide’s effect on fibrosis, the outcomes hinted at its potential as a meaningful treatment across all doses tested.

Dr. Rohit Loomba from the University of California San Diego School of Medicine underscored the urgency for new therapies for MASH, the second leading cause of liver transplants in the U.S. He noted that the study's findings are promising for addressing the progression of MASH and reducing its associated severe health complications.

The safety profile of tirzepatide in SYNERGY-NASH was consistent with previous trials, namely SURMOUNT and SURPASS, primarily featuring mild to moderate gastrointestinal side effects such as nausea, diarrhea, decreased appetite, constipation, and weight loss.

Dr. Jeff Emmick, Eli Lilly’s Senior Vice President of Product Development, expressed satisfaction with the results, noting the substantial MASH resolution and fibrosis improvement. He highlighted the impending impact of MASH on millions of adults in the U.S. and the potential of tirzepatide to assist those affected. Eli Lilly is actively engaging regulators to discuss the next steps for tirzepatide in treating MASH.

SYNERGY-NASH was a rigorously controlled phase 2 trial, evaluating tirzepatide at 5 mg, 10 mg, and 15 mg doses against a placebo in adults with biopsy-confirmed MASH and stage 2 or 3 fibrosis over a 52-week period. The trial's primary endpoint focused on MASH resolution without worsening fibrosis, while secondary endpoints included the improvement of fibrosis without exacerbating MASH.

Tirzepatide, a novel GIP and GLP-1 receptor agonist, is administered weekly and has demonstrated efficacy in reducing food intake and modulating fat utilization. It's currently explored for various conditions, including obesity, heart failure, obstructive sleep apnea, and chronic kidney disease. The FDA has approved tirzepatide under the brand names Mounjaro® for type 2 diabetes management and Zepbound® for obesity and weight-related comorbid conditions, both as an adjunct to diet and exercise.

These findings support tirzepatide's potential role in managing MASH, marking a significant step forward in addressing a critical unmet need in liver disease treatment.