Novo Nordisk today announced results from part 1 of the ongoing Phase 3 ESSENCE trial. Part 1 evaluated the effect of once-weekly subcutaneous semaglutide 2.4 mg on liver tissue (histology) compared with placebo in people with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (stage 2 or 3).⁴ Results were presented at the 75^th American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting^®.

At Week 72, primary endpoints showed 62.9% of people treated with semaglutide 2.4 mg achieved resolution of steatohepatitis with no worsening of liver fibrosis compared to 34.1% on placebo. 37.0% of people treated with semaglutide 2.4 mg achieved improvements in liver fibrosis with no worsening of steatohepatitis compared to 22.5% on placebo. Overall, secondary endpoints showed 32.8% of patients treated with semaglutide 2.4 mg achieved both resolution of steatohepatitis with improvements in liver fibrosis (as compared to 16.2% of patients on placebo).¹

"These initial data shared at The Liver Meeting^® demonstrated that semaglutide 2.4 mg slowed MASH progression and reversed existing liver damage," said Arun Sanyal, MD, principal investigator of the study, and Director, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University. "The ESSENCE data may represent key findings for patients in the treatment of MASH, which is estimated to affect about one in 20 adults in the US."

In addition to meeting both primary endpoints, secondary endpoints showed histological benefits were reflected in improvements of pre-specified non-invasive tests (NITs) in people treated with semaglutide 2.4 mg vs placebo. The additional data showed improvements in liver enzymes (including ALT, AST, and GGT), as well as the Enhanced Liver Fibrosis (ELF)™ test. In the trial, semaglutide 2.4 mg appeared to have a safety profile similar to previous semaglutide 2.4 mg trials in other therapeutic area patient populations.¹

"We are pleased by the ESSENCE data presented at AASLD, which supports the growing clinical evidence of semaglutide 2.4 mg for people living with chronic conditions like MASH," said Anna Windle, PhD, senior vice president of Clinical Development, Medical & Regulatory Affairs at Novo Nordisk. "These data are a cornerstone in our research and build on our understanding of how MASH and cardiometabolic conditions like type 2 diabetes, obesity, dyslipidemia, and high blood pressure are interrelated."

Semaglutide 2.4 mg is not approved in the US to treat MASH. Novo Nordisk expects to file for regulatory approvals in the US in the first half of 2025.

About ESSENCE (semaglutide 2.4 mg)
ESSENCE is a Phase 3 trial evaluating the effect of once-weekly subcutaneous semaglutide 2.4 mg in adults with metabolic dysfunction-associated steatohepatitis with moderate to advanced liver fibrosis (stage 2 or 3). It is a two-part trial where 1,200 planned participants were randomized 2:1 to receive semaglutide 2.4 mg or placebo, on top of standard of care for 240 weeks. In part 1, the objective was to demonstrate that treatment with semaglutide 2.4 mg improves liver histology at 72 weeks based on biopsy sampling from the first 800 randomized patients. In part 2, the objective is to demonstrate that treatment with semaglutide 2.4 mg lowers the risk of liver-related clinical events compared to placebo in adults with MASH and moderate to advanced liver fibrosis at 240 weeks.⁴

About metabolic dysfunction-associated steatohepatitis (MASH)
MASH is a chronic, progressive, metabolic disease affecting the liver, which can be potentially life-threatening if not properly managed.^5,6 Among people who are overweight or obese, more than one in three also have MASH.⁷ Excess fat can build up in the liver, which over time, can lead to inflammation and severe scarring of the liver.⁸ People living with MASH often experience few or no specific symptoms in the early stages of the disease, which often results in delayed diagnosis.⁹ One in 20 adults in the United States are living with MASH.² The disease progresses to cirrhosis in approximately 20% of cases.³ MASH is a leading cause of cirrhosis in adults in the US, and MASH-related cirrhosis is the second indication for liver transplants in the country.¹⁰

About Novo Nordisk
Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With U.S. headquarters in New Jersey and commercial, production, and research facilities in seven states plus Washington DC, Novo Nordisk employs approximately 8,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, X, LinkedIn and YouTube. 

References

1. Newsome PN, Sanyal AJ, Kliers I, et al. Phase 3 ESSENCE Trial: Semaglutide in metabolic dysfunction-associated steatohepatitis (MASH]. Presented at The Liver Meeting®, American Association for the Study of Liver Diseases 2024, Nov 19, 2024. 
2. Younossi ZM, Mangla KK, Chandramouli AS, et al. Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH. Hepatol Commun. 2024;8:e0488. doi:10.1097/HC9.0000000000000488
3. Sheka AC, Adeyi O, Thompson J, et al. Nonalcoholic Steatohepatitis: A Review JAMA. 2020;323:1619. doi: 10.1001/jama.2020.5249
4. Newsome PN, Sanyal AJ, et al. Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial. Aliment Pharmacol Ther. 2024;10:18331. doi:10.1111/apt.18331 
5. Ilan Y. Analogy between non-alcoholic steatohepatitis (NASH) and hypertension: a stepwise patient-tailored approach for NASH treatment. Ann Gastroenterol. 2018;31:296-304. doi:10.20524/aog.2018.0248
6. Tesfay M, Goldkamp JW, Neuschwander-Tetri BA. NASH: The Emerging Most Common Form of Chronic Liver Disease. Mo Med. 2018;115:225-229.
7. Quek J, Chan KE, Wong ZY, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8:20-30. doi: 10.1016/S2468-1253(22)00317-X
8. National Institute of Diabetes and Digestive and Kidney Diseases. Definition & Facts of NAFLD & NASH. Accessed November 7, 2024. Available at: https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts
9. Verywell Health. MASH overview. Accessed November 5, 2024. Available at: https://www.verywellhealth.com/non-alcoholic-steatohepatitis-nash-5196357
10. Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol. 2024. doi:10.3350/cmh.2024.0431

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