On November 1, 2024, Novo Nordisk announced the headline results from Part 1 of its ongoing Phase 3 ESSENCE trial. Results shows that semaglutide 2.4 mg significantly improved liver fibrosis and resolved metabolic dysfunction-associated steatohepatitis (MASH) in patients compared to a placebo. Following the positive data, Novo Nordisk plans to submit approval applications to regulators in the US and Europe in the first half of 2025. Detailed data from the ESSENCE trial will be presented at an upcoming scientific conference. Part 2 of the trial will continue, with results expected in 2029.
The ESSENCE trial is a Phase 3 study designed to evaluate the efficacy and safety of once-weekly semaglutide 2.4 mg compared to a placebo in adults with MASH and moderate to advanced liver fibrosis (Stage 2 or 3). The trial consists of two parts, enrolling 1,200 participants who were randomised 2:1 to receive semaglutide 2.4 mg or placebo for up to 240 weeks, along with standard care for MASH. In part 1, the objective was to demonstrate that treatment with semaglutide 2.4 mg improves liver histology at 72 weeks based on biopsy sampling from the first 800 randomised patients. In part 2, the objective is to demonstrate that treatment with semaglutide 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.
The trial achieved its primary endpoints. Compared to placebo, semaglutide 2.4 mg demonstrated a statistically significant and superior improvement in liver fibrosis with no worsening of steatohepatitis, as well as resolution of steatohepatitis with no worsening of liver fibrosis. At Week 72, 37.0% of patients in the semaglutide 2.4 mg group showed improvement in liver fibrosis without worsening of steatohepatitis, compared to 22.5% in the placebo group. Additionally, 62.9% of patients in the semaglutide 2.4 mg group achieved steatohepatitis resolution without fibrosis worsening, compared to 34.1% in the placebo group.
In the trial, semaglutide 2.4 mg appeared to have a safe and well-tolerated profile in line with previous semaglutide 2.4 mg trials.
About MASH & Other Therapies
MASH is a serious and progressive metabolic condition affecting over 250 million people worldwide. By 2030, the number of individuals with advanced stages of the disease is expected to double. Among people who are overweight or obese, more than one-third are also affected by MASH. Often, patients show few or no specific symptoms in the early stages, which can lead to delayed diagnosis. Compared to the general population, people with MASH face a higher risk of progressing to advanced liver disease, including liver cancer. Currently, only one targeted therapy is approved for MASH.
On March 14, 2024, the FDA approval of Madrigal’s Resmetirom marked a significant milestone in MASH treatment, addressing a critical gap in the field. In just six months, Resmetirom’s revenue skyrocketed, climbing from $14.6 million in Q2 to $62.2 million in Q3, underscoring the strong market demand for MASH therapies.
Figure 1. Sales of Resmetirom
Read more: FDA Approves First NASH Drug & Other Pipelines in Clinical Trials
Beyond Resmetirom, several GLP-1 candidates are emerging as competitors in the MASH treatment landscape. These include Survodutide (BI 456906), a dual GCG/GLP-1 receptor agonist developed jointly by Boehringer Ingelheim and Zealand Pharma, as well as Lilly's Tirzepatide and Retatrutide.
Read more: Upcoming GLP-1 RAs for NASH: A Comprehensive List
With the global rise in obesity and diabetes, MASH has emerged as a critical public health concern. The competitive landscape for treatments in this field reflects an urgent response to address this unmet medical need. Key factors shaping a drug’s market potential include efficacy, safety, tolerability, and long-term health impacts. The promising results for semaglutide in the ESSENCE trial not only bring new hope to patients but also set a higher standard for industry treatment options. As further clinical data becomes available and new drugs enter the market, the MASH treatment landscape will continue to transform.
References:
Novo Nordisk A/S: Semaglutide 2.4 mg demonstrates superior improvement in both liver fibrosis and MASH resolution in the ESSENCE trial. Retrieved November 1, 2024 from https://www.globenewswire.com/news-release/2024/11/01/2973330/0/en/Novo-Nordisk-A-S-Semaglutide-2-4-mg-demonstrates-superior-improvement-in-both-liver-fibrosis-and-MASH-resolution-in-the-ESSENCE-trial.html