Core Insights - Novo Nordisk's semaglutide (Wegovy) has received FDA approval for a supplemental new drug application (sNDA) to treat metabolic dysfunction-associated steatotic liver disease (MASH) in patients with moderate to advanced liver fibrosis (F2 or F3) [1][2] - The approval is based on positive results from the Phase III ESSENCE study, which demonstrated significant improvements in liver fibrosis and steatohepatitis without worsening conditions [2][3] - The MASH indication represents a significant opportunity for GLP-1 drugs, with a large unmet clinical need and a projected market capacity exceeding $10 billion by 2025, growing at a compound annual growth rate (CAGR) of 20.19% from 2016 to 2025 [4][5] Group 1: Drug Approval and Study Results - The FDA approval was based on the ESSENCE study, a 240-week randomized, double-blind, placebo-controlled trial involving 1,200 patients [2] - Part 1 of the study showed that 36.8% of patients treated with 2.4 mg semaglutide experienced significant liver fibrosis improvement compared to 22.4% in the placebo group [3] - The study also indicated that 62.9% of the semaglutide group had resolution of steatohepatitis without worsening fibrosis, compared to 34.3% in the placebo group [3] Group 2: Market Context and Competitive Landscape - MASH is a critical area of focus for GLP-1 drugs, with significant unmet clinical needs and strong correlations with metabolic diseases [4][5] - Novo Nordisk's semaglutide is the first and currently the only GLP-1 drug approved for MASH, enhancing its competitive position in the market [3][5] - In the first half of the year, Novo Nordisk reported sales of 112.756 billion Danish Krone for semaglutide, leading the market significantly ahead of competitors [5]

Core Viewpoint - Altimmune, Inc. announced positive preliminary results from the IMPACT 2b clinical trial of its candidate drug pemvidutide for the treatment of Metabolic Associated Steatotic Liver Disease (MASH), but the efficacy disappointed investors, leading to a significant drop in stock price [2]. Group 1: Clinical Trial Results - The trial recruited 212 participants diagnosed with MASH at F2/F3 fibrosis stages, with a low dropout rate of only 9% [6]. - In the intention-to-treat (ITT) analysis, 59.1% of the 1.2 mg group and 52.1% of the 1.8 mg group achieved MASH resolution without worsening fibrosis, significantly higher than the 19.1% in the placebo group (both p<0.0001) [10]. - For fibrosis improvement without worsening MASH, the improvement rates were 31.8% and 34.5% for the treatment groups, compared to 25.9% for the placebo, but the differences were not statistically significant [11]. - AI-assisted analysis showed that 30.6% of the 1.8 mg group had a fibrosis reduction of over 60%, significantly better than the 8.2% in the placebo group (p<0.001) [12]. - The treatment groups showed significant improvements in non-invasive fibrosis assessment indicators compared to the placebo [13]. Group 2: Weight Control and Tolerability - The average weight loss for the 1.2 mg and 1.8 mg groups was 5.0% and 6.2%, respectively, compared to only 1.0% in the placebo group (both p<0.001) [14]. - The overall tolerability of the drug was good, with only 0.0% and 1.2% of participants in the treatment groups discontinuing due to adverse reactions, lower than the 2.4% in the placebo group [16]. - No serious adverse events related to the treatment were reported [17]. Group 3: Expert Commentary - The CEO of Altimmune expressed confidence in pemvidutide's potential to change the treatment landscape for MASH, a condition expected to affect over 27 million people in the U.S. by 2030 [9]. - An expert noted that achieving MASH resolution and weight loss within 24 weeks is uncommon among similar drugs, highlighting pemvidutide's superior tolerability and low discontinuation rate [9]. - The results indicate a promising trend for fibrosis improvement, and the company plans to advance to Phase 3 trials following a successful Phase 2 meeting with the FDA in Q4 2025 [9].