Novo's Wegovy Secures FDA Approval for MASH, Challenging Madrigal's Rezdiffra in Liver Disease Market

Novo Nordisk's blockbuster drug Wegovy (semaglutide) has received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) in adults with moderate to advanced fibrosis. This landmark decision marks Wegovy's third indication and positions it as a direct competitor to Madrigal Pharmaceuticals' Rezdiffra in the burgeoning MASH market.

Wegovy's MASH Approval: A Game-Changer for Liver Disease Treatment

The FDA's green light for Wegovy in MASH is based on promising results from the first part of Novo Nordisk's two-part clinical trial, Essence. The study demonstrated significant improvements in both MASH resolution and liver fibrosis reduction. Specifically, 63% of patients receiving Wegovy achieved resolution of steatohepatitis without worsening fibrosis at 72 weeks, compared to 34% in the placebo group. Additionally, 37% of Wegovy-treated patients showed improvement in liver fibrosis without worsening steatohepatitis, versus 22% in the control arm.

MASH, previously known as nonalcoholic steatohepatitis (NASH), affects an estimated 1 in 20 people in the United States and approximately 1 in 3 overweight or obese individuals globally. If left untreated, MASH can progress to severe complications such as cirrhosis, liver cancer, and the need for liver transplantation.

Market Implications and Competitive Landscape

Wegovy's approval in MASH sets the stage for a competitive showdown with Madrigal Pharmaceuticals' Rezdiffra, which made history in March as the first FDA-approved MASH treatment. While both drugs target similar patient populations, they differ in their mechanisms of action. Wegovy, a GLP-1 receptor agonist, is thought to improve MASH through anti-inflammatory effects and liver fat reduction. In contrast, Rezdiffra is a thyroid receptor-beta agonist that directly targets the liver.

Despite entering the market second, industry analysts believe there is ample room for multiple players in the MASH treatment landscape. Madrigal's Rezdiffra has already demonstrated strong market performance, consistently beating sales expectations since its launch. In the second quarter of 2025, Rezdiffra reported impressive sales of $212.8 million.

The MASH market is poised for further expansion, with other pharmaceutical giants, including Eli Lilly, advancing their own candidates. Lilly's tirzepatide, a dual GIP/GLP-1 medication, has shown promising results in mid-stage trials, with up to 54.9% of patients experiencing improved fibrosis without MASH worsening.

Looking Ahead: Global Expansion and Ongoing Research

Novo Nordisk is not resting on its laurels, having filed for Wegovy MASH approvals in the European Union and Japan. The company continues to conduct the second part of the Essence trial, with results expected around 2029. These ongoing studies will provide further insights into Wegovy's long-term efficacy and safety profile in MASH patients.

As the MASH treatment landscape evolves, the pharmaceutical industry eagerly anticipates the impact of these groundbreaking therapies on patient outcomes and market dynamics. With multiple players entering the field, patients with this severe liver disease may soon have access to a range of innovative treatment options.