Novo Nordisk GLP-1 Drug Achieves MASH Trial Goals, Paving Way for FDA & EMA Filings

Novo Nordisk's obesity drug, Wegovy, has successfully met the primary objectives of a critical trial targeting metabolic dysfunction steatohepatitis (MASH), an accomplishment that could pave the way for the drug’s expanded use. MASH is a severe condition characterized by the accumulation of liver fat, leading to deteriorating liver function and, in advanced stages, necessitating liver transplants. Globally, over 250 million individuals are believed to suffer from this ailment.

Wegovy’s active component, semaglutide, is an engineered peptide designed to bind to the GLP-1 receptor, initiating various metabolic activities. Initially, semaglutide was approved for managing type 2 diabetes, marketed under the name Ozempic.

The promising results, reported on Friday, emerge from a placebo-controlled Phase 3 trial involving 1,200 participants with MASH and moderate-to-advanced liver fibrosis (scarring). After 72 weeks of treatment, Novo Nordisk revealed that 37% of the participants administered weekly doses of Wegovy, in addition to standard care, exhibited improvement in liver fibrosis without further aggravation of the fatty liver disease. In contrast, only 22.5% of those receiving a placebo alongside standard care reached this milestone.

Additionally, Novo Nordisk reported that 62.9% of patients in the Wegovy group experienced a resolution of fatty liver disease without worsening liver fibrosis. By comparison, 34.1% of those in the placebo group achieved similar results. The findings were statistically significant, according to the company. On safety and tolerability measures, Wegovy's performance was consistent with previous trials of the drug. Detailed results are expected to be shared at a medical conference later this year.

These findings are derived from the first part of a two-part Phase 3 study. The second part will assess the long-term impact of Wegovy on the risk of liver-related clinical events compared to a placebo over a 240-week period. Novo Nordisk anticipates that data from Part 2 will be available in 2029. However, based on the current clinical data, the company plans to apply for approval of Wegovy for MASH in the U.S. and European Union in the first half of the upcoming year.

In an investor note, Leerink Partners analyst Thomas Smith stated that the data aligns closely with their best-case scenario, showing significant improvement in fibrosis but not a revolutionary outcome. Leerink posits that peptide drugs, such as Wegovy, can effectively address some aspects of MASH and its associated conditions, including obesity, type 2 diabetes, and cardiovascular diseases. Nonetheless, Smith noted that these drugs are not a definitive cure for MASH patients with advanced fibrosis and predicted that a combination of medications would likely become the standard treatment in the future.

William Blair analyst Andy Hsieh observed that the extent of fibrosis improvement with Wegovy parallels that of Rezdiffra, a drug developed by Madrigal Pharmaceuticals, which was the first FDA-approved treatment for MASH earlier this year. The improvement in fibrosis without disease progression was 12% for the daily pill Rezdiffra compared to 14% for the weekly injectable Wegovy.

Earlier this year, both Eli Lilly and Boehringer Ingelheim reported encouraging clinical trial results for their potential MASH treatments. Hsieh indicated that the investment community generally agrees that GLP-1 receptor agonists will likely be integrated into the MASH treatment regimen. He emphasized that the recent developments with Wegovy strengthen the growing body of evidence supporting this trend.