Eli Lilly and Company (NYSE: LLY) revealed compelling outcomes from the SYNERGY-NASH study, showcasing significant efficacy of tirzepatide in treating metabolic dysfunction-associated steatohepatitis (MASH) with advanced fibrosis. The phase 2 trial demonstrated that tirzepatide, in varying dosages, successfully met the primary endpoint, with a substantial percentage of participants achieving MASH resolution without worsening fibrosis after 52 weeks of treatment.

The study, conducted among 190 patients with or without type 2 diabetes, tested the effects of 5 mg, 10 mg, and 15 mg doses of tirzepatide. Results were profound: 51.8%, 62.8%, and 73.3% of participants for each respective dosage achieved MASH resolution, compared to just 13.2% of those on a placebo. These findings were recently presented at the European Association for the Study of the Liver (EASL) Congress 2024 and concurrently published in The New England Journal of Medicine (NEJM).

Detailed Study Findings

Tirzepatide not only addressed the primary endpoint but also showed promising results in secondary metrics. A significant portion of participants across all dosages reported a one-stage or greater improvement in fibrosis, without MASH worsening—59.1%, 53.3%, and 54.2% respectively—outperforming the 32.8% placebo response. The trial also noted improvements in body weight, liver injury markers, and other biomarkers indicating reductions in liver fat, inflammation, and fibrosis.

Clinical and Strategic Implications

“MASH is the second most common cause of liver transplants in the U.S., underscoring the critical need for effective treatment options,” stated Dr. Rohit Loomba, MD, MHSc, chief of the division of gastroenterology and hepatology at the University of California San Diego School of Medicine. Dr. Loomba highlighted the significance of the SYNERGY-NASH results, emphasizing the potential of tirzepatide to slow disease progression and possibly reduce severe health complications.

Eli Lilly’s senior vice president of product development, Dr. Jeff Emmick, MD, PhD, expressed optimism about the trial outcomes, considering the potential benefits for the over 19 million U.S. adults projected to be affected by MASH by 2039. The company is currently discussing next steps with regulatory authorities, aiming to expand tirzepatide’s indications to include MASH treatment, following its previous approvals for type 2 diabetes and obesity management.

The Future of Tirzepatide

Tirzepatide, a dual GIP and GLP-1 receptor agonist, continues to be studied extensively. Its implications extend beyond MASH, with ongoing research exploring its potential in managing conditions like chronic kidney disease and obesity-related comorbidities. The compound’s ability to modulate appetite and fat utilization through incretin hormone receptors could revolutionize treatment paradigms across multiple metabolic disorders.

Eli Lilly’s SYNERGY-NASH trial marks a significant milestone in the management of metabolic dysfunction-associated steatohepatitis. As tirzepatide progresses through clinical trials and regulatory discussions, its potential to improve the lives of those with serious metabolic diseases continues to grow. This study not only reinforces the drug’s efficacy but also aligns with broader health management goals, potentially setting a new standard in MASH therapy.

  EASL Congress, Eli Lilly, Lilly, MASH treatment, metabolic dysfunction-associated steatohepatitis, Phase 2 Study, SYNERGY-NASH, Tirzepatide