Topline Findings
- Wegovy FDA Approval: Accelerated approval granted for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis, marking the first GLP-1 receptor agonist approved for this indication.
- ESSENCE Trial Results: Phase III data show 63% of patients achieved MASH resolution with no worsening of fibrosis and 37% improved fibrosis with no worsening of steatohepatitis.
- Market and Public Health Impact: Approval highlights unmet medical need, potential global prevalence growth, and positions Wegovy as a treatment option in a condition affecting one in 20 adults in the United States.
On Friday, the FDA granted accelerated approval for a new indication of Novo Nordisk’s Wegovy (semaglutide) causing the company’s share price to jump approximately 5% as of the time of publication. The GLP-1 receptor agonist’s new indication is for adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis, but not cirrhosis.
The regulatory action marks the first and only GLP-1 receptor agonist to be approved for these indications. Approval was based on results from the Phase III ESSENCE trial (NCT04822181), which showed that patients treated with Wegovy demonstrated significant improvements in both steatohepatitis resolution and liver fibrosis compared with placebo at 72 weeks.1
How Could Wegovy Change the Treatment of Adults with Noncirrhotic MASH?
"Today's decision by the FDA reflects the continued progress in how we understand and treat patients with MASH, bringing us closer to care that meets the needs of people living with this disease," said Arun Sanyal, MD, director, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, in a press release. "If left untreated, MASH can lead to serious and potentially fatal outcomes. The clinical evidence seen in ESSENCE underscores the promise of this approach to treating adults with MASH with moderate to advanced liver fibrosis."
ESSENCE Trial Design and Key Results
- The interventional, randomized, two-part ESSENCE trial evaluated the effect of once-weekly subcutaneous Wegovy 2.4 mg in 1,197 patients with MASH with moderate to advanced liver fibrosis.
- Patients were randomly assigned in a 2:1 ratio to receive either Wegovy or placebo in addition to standard of care for 240 weeks.
- The primary endpoint of part 1 was to demonstrate that Wegovy improves liver histology compared to placebo.
- The primary endpoint of part 2, which is still in progress, is to demonstrate Wegovy lowers the risk of liver-related clinical events compared to placebo at 240 weeks.
- Key secondary endpoints include but are not limited to change in body weight, progression of liver fibrosis, change in alanine aminotransferase, and change in aspartate aminotransferase.2
- Results showed that 63% of patients treated with Wegovy achieved MASH resolution with no worsening of fibrosis compared to 34% in the placebo group.
- Thirty-seven percent achieved fibrosis improvement with no worsening of steatohepatitis compared to 22% in the placebo group.
- At week 72, 33% of patients treated with Wegovy achieved both resolution of steatohepatitis and improvement in liver fibrosis compared to 16% in the placebo group.1
Market Reaction
Shares of Novo Nordisk climbed following the approval, reflecting the significance of Wegovy’s expanded role in addressing a condition with limited treatment options. As of 10:30 A.M. this morning, shares were up 4.70% to about $54 per share.3
MASH Prevalence and Unmet Need
MASH affects up to one in 20 people in the United States, and more than a quarter of these cases may already involve cirrhosis.1 The overall prevalence of MASH is expected to increase by an estimated 63% by 2030. While it is more common in adults, children can also develop MASH.4
Novo Nordisk Perspective
"For far too long, this disease has remained unrecognized, undiagnosed, and often untreated, despite impacting so many people," said Dave Moore, EVP, US operations, Novo Nordisk, in the press release. "The FDA's conditional approval of Wegovy for the treatment of adults with noncirrhotic MASH marks a truly pivotal milestone and a significant step forward for the MASH community and those seeking new options. This builds on the expanding body of evidence demonstrating the clinical benefits of semaglutide across a range of chronic conditions including diabetes, obesity, cardiovascular and chronic kidney disease."
References
- Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. PR Newswire. August 15, 2025. Accessed August 18, 2025. https://www.prnewswire.com/news-releases/wegovy-approved-by-fda-for-the-treatment-of-adults-with-noncirrhotic-mash-with-moderate-to-advanced-liver-fibrosis-302531394.html
- Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH) (ESSENCE). Clinicaltrials.gov. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04822181?utm_source=chatgpt.com
- Novo Nordisk A/S. Google Finance. Accessed August 18, 2025. https://www.google.com/finance/quote/NVO:NYSE?sa=X&ved=2ahUKEwiAlPr_xJSPAxWlhIkEHSLbLJ8Q3ecFegQIMhAb
- MASH 101: What You Need to Know About an Emerging Liver Disease. HealthWell Foundation. Accessed August 18, 2025. https://www.healthwellfoundation.org/realworldhealthcare/mash-101-what-you-need-to-know-about-an-emerging-liver-disease/
