Novo Nordisk Wegovy approved by USFDA for adults with noncirrhotic MASH with liver fibrosis

This FDA approval is based on results from the phase 3 ESSENCE trial investigating the effects of once-weekly Wegovy 2.4 mg injection on liver histology in adults with MASH and moderate to advanced liver fibrosis (stage F2 to F3) at Week 72. The first primary endpoint showed 63% of people treated with Wegovy 2.4 mg injection (n=534) achieved resolution of steatohepatitis and no worsening of liver fibrosis compared to 34% on placebo (n=266) with a statistically significant difference in response rate vs placebo of 29 (95% CI, 21;36). Additionally, the second primary endpoint showed 37% of people treated with Wegovy 2.4 mg achieved improvement in liver fibrosis and no worsening of steatohepatitis compared to 22% on placebo with a statistically significant difference in response rate vs placebo of 14 (95% CI, 8;21). A confirmatory secondary endpoint at Week 72 showed 33% of patients treated with Wegovy 2.4 mg achieved both resolution of steatohepatitis and improvement in liver fibrosis compared to 16% on placebo with a statistically significant difference in response rate vs placebo of 17 (95% CI, 10;23). A total of 83.5% of the patients in the semaglutide group maintained the target dose of 2.4 mg until Week 72.

"The 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. "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."

MASH represents a significant health burden in the US, affecting approximately one in 20 people. People living with MASH are often asymptomatic or present with nonspecific symptoms in the early stages of the disease, which may result in a delayed diagnosis. Left untreated, MASH can progress to serious and even fatal outcomes, such as cirrhosis, liver cancer, and the need for liver transplant. Among people who are living with overweight or obesity worldwide, one in three also have MASH.

"For far too long, this disease has remained unrecognized, undiagnosed, and often untreated, despite impacting so many people," said Dave Moore, executive vice president of US Operations, at Novo Nordisk. "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."

The FDA initially approved Wegovy in 2021 with a reduced calorie meal plan and increased physical activity to help adults with obesity, or some adults with excess weight (overweight) who also have weight-related medical problems to lose weight and keep the weight off. The indication was expanded in 2022 to include children aged 12 years and older with obesity. In 2024, Wegovy was approved to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and either obesity or overweight. Now, the FDA has granted accelerated approval for Wegovy for a new patient population to treat adults with MASH with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver.

In February 2025, Novo Nordisk also filed for regulatory approval in the EU, followed by regulatory submission in Japan in May 2025.