Novo Nordisk's Late-Stage MASH Win Boosts GLP-1 Expansion

A day after Madrigal Pharmaceuticals made headlines, Novo Nordisk stepped into the limelight by announcing promising results from a Phase 3 trial for semaglutide, a medication aimed at treating metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease. Novo Nordisk, a Danish pharmaceutical giant, already markets semaglutide under the brand names Wegovy for obesity and Ozempic for type 2 diabetes.

The Phase 3 study, known as the ESSENCE trial, showed that patients receiving a 2.4 mg dose of semaglutide experienced significant improvements in liver fibrosis without a worsening of steatohepatitis. Additionally, the trial met its primary endpoints by demonstrating a resolution of steatohepatitis without worsening of liver fibrosis. At the 72-week point, 37% of patients treated with semaglutide showed improvement in liver fibrosis compared to 22.5% in the placebo group. Furthermore, 62.9% of patients on semaglutide experienced a resolution of steatohepatitis, compared to 34.1% on placebo.

Novo Nordisk reported that semaglutide was safe and well-tolerated, consistent with the drug's profile in other trials. The company plans to seek regulatory approval in the United States and the European Union during the first half of 2025 and aims to present the trial data at a scientific meeting later this year. The second phase of the ESSENCE study is expected to yield results in 2029.

The anticipation surrounding this readout was high among MASH drug developers, especially given the rising prominence of the GLP-1 class of medications. The results come shortly after Madrigal Pharmaceuticals reported impressive third-quarter sales of $62.2 million for its MASH-specific drug, Rezdiffra, which was approved earlier this year. Despite the strong sales figures, there remains uncertainty among analysts about whether insurers might require patients to use a GLP-1 drug before switching to a MASH-specific treatment.

During Madrigal's earnings call, CEO Bill Sibold addressed these concerns by stating that there had been no indications of insurers mandating a step-through process so far. He emphasized that while topline readouts do not always translate seamlessly into treatment labels, the company remains optimistic about the future. Sibold added that the ongoing trial results would likely influence payer decisions moving forward.

Following these developments, Madrigal's stock experienced a significant boost, rallying about 18% after an initial premarket selloff. Since the end of Wednesday, the company's shares have climbed by 41%.

The new data from Novo Nordisk represent a turnaround after semaglutide failed to meet similar primary endpoints in a Phase 2 study last year. The high prevalence of MASH among individuals with obesity has made it a critical area of focus for companies developing GLP-1 drugs. Despite the high cost of these medications in the United States, their annual list prices are still lower than Rezdiffra's wholesale acquisition cost of $47,400 per year. However, GLP-1 drugs have faced challenges such as inconsistent insurance coverage and high dropout rates.

Sibold remains confident that payers will continue to support Rezdiffra, which is the first FDA-approved treatment targeting the root cause of MASH. He expressed optimism about the company's position ahead of any potential outcomes from the ESSENCE trial.