Wegovy Demonstrates Superiority Over Placebo in Patients with Metabolic Dysfunction-Associated Steatohepatitis

Image Credit: Adobe Stock Images/ArtemisDiana

Results from part one of the Phase III ESSENCE trial demonstrated that Novo Nordisk’s Wegovy (semaglutide) 2.4 mg was significantly superior to placebo in treating patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (stage 2 or 3). According to the company, detailed results of the trial will be presented at a scientific conference this year, as part two is ongoing with expected readout in 2029.¹

“We are very pleased about the ESSENCE clinical trial results and the potential of semaglutide to help people living with MASH” said Martin Holst Lange, EVP, head of development, Novo Nordisk, in a press release. “Among people with overweight or obesity, one in three live with MASH. This has a serious impact on their health and represents a significant unmet need.”

ESSENCE is a two-part clinical trial evaluating the effect of once-weekly subcutaneous Wegovy 2.4 mg. As part of the trial, 1,200 patients were randomly assigned in a 2:1 ratio to receive Wegovy 2.4 mg or placebo, on top of standard of care for 240 weeks. In part one, the primary endpoint was to demonstrate that treatment with Wegovy 2.4 mg improves liver histology at 72 weeks based on biopsy sampling from the first 800 randomized patients. In part two, the primary endpoint is to demonstrate that treatment with Wegovy 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.

Results found that at week 72, 37% of patients treated with Wegovy demonstrated improvement in liver fibrosis with no worsening of steatohepatitis compared to 22.5% on placebo. Additionally, 62.9% of people treated with Wegovy 2.4 mg achieved resolution of steatohepatitis with no worsening of liver fibrosis compared to 34.1% on placebo.

The safety profile of Wegovy was consistent with previous findings, showing it to be well tolerated.¹ Common adverse effects associated with Wegovy include nausea; diarrhea; vomiting; constipation; stomach pain; headache; tiredness upset stomach; dizziness; feeling bloated; belching; low blood sugar in people with type 2 diabetes; gas; stomach flu; heartburn; and runny nose or sore throat.²

According to Novo Nordisk, over 250 million people live with MASH and the number of individuals in advanced stages of the disease is expected to double by 2030. Currently more than one in every three people who are overweight or living with obesity are also living with MASH. Those living with MASH have a higher risk of progression to advanced liver disease, including liver cancer.¹

According to the HealthWell Foundation, anywhere from 1.5% to 6.5% of adults in the United States are currently living with MASH. The prevalence of MASH is expected to increase 63% by 2030, which will result in it becoming the leading cause of liver transplants in the United States by next year.³

“Patients, providers, scientists, non-profits, and advocates in the worldwide liver community came together last year to modify the way we talk about NASH—now MASH—in an effort to better identify who has the disease or is at risk for the disease,” said Lorraine Stiehl, CEO, American Liver Foundation, speaking to HealthWell Foundation. “The name change also removes some of the stigma associated with the terms ‘fatty’ and ‘alcoholic,’ which can create barriers to screening, diagnosis and appropriate treatment through medications and lifestyle modification.”

Novo Nordisk plans regulatory submissions in the United States and Europe by mid-2025.¹

References

1. Novo Nordisk A/S: Semaglutide 2.4 mg demonstrates superior improvement in both liver fibrosis and MASH resolution in the ESSENCE trial. Novo Nordisk. November 1, 2024. Accessed November 1, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=171971

2. Keeping an eye on common side effects. Wegovy. Accessed November 1, 2024. https://www.wegovy.com/dashboard/my-library/week-02-tips-for-managing-common-side-effects.html#:~:text=Common%20side%20effects%20of%20Wegovy,runny%20nose%20or%2sore%20throat. Effect

3. MASH 101: What You Need to Know About an Emerging Liver Disease. HealthWell. August 7, 2024. Accessed November 1, 2024. https://www.healthwellfoundation.org/realworldhealthcare/mash-101-what-you-need-to-know-about-an-emerging-liver-disease/#:~:text=According%20to%20ALF%2C%20about%20100,first%2Dever%20study%20on%20NAFLD.