Metabolic dysfunction-associated steatohepatitis (MASH) is classified as a severe, progressive, and dangerous liver-related metabolic disorder that can lead to death if left untreated.
It is estimated that over 250 million individuals are affected by MASH and the number of people at an advanced stage of the disease is likely to increase two-fold by 2030. Among the overweight or obese populations, MASH prevalence is found to be greater than one-third of the patients.
Those with MASH in most cases do not show or have no symptoms in the early stages of the illness hence the long gaps in between before diagnosis is made.
There is an increased risk of hepatic disease progression, including that associated with hepatocellular carcinoma, among individuals with MASH as compared to the general population.Â
Wegovy® is a branded medication, which contains a weekly subcutaneous semaglutide 2.4 mg. It is a GLP-1 receptor agonist. Wegovy® is approved for use as an adjunct to a reduced calorie intake as well as increased exercise for long-term weight control in adults with a body mass index of 30 kg/m2 or more, adults with a body mass index of 27kg/m2 or more with at least one weight-related comorbid condition.
It is also indicated in pediatric patients 12 years of age and older with a certain body mass index (95 percentile) or higher based on age and gender (obesity).Â
In the United States, Wegovy® is taken with a modified calorie intake and increased exercise with the purpose of preventing the occurrence of major adverse cardiovascular events (MACE) in patients with cardiovascular disease who are either obese or overweight, as well as facilitating weight loss and its long-term maintenance in adults and children twelve years and older who are obese and in adults who are overweight with at least one weight-related associated medical condition.Â
Novo Nordisk today reported on the ESSENCE trial’s study part 1 results, which was a phase 3 trial of 240 weeks duration and double blinded in 1,200 patients suffering from metabolic dysfunction associated steatohepatitis (MASH) with moderate to severe liver fibrosis (stage 2 or stage 3).
Part 1 of the ESSENCE trial evaluated the effect of once-weekly semaglutide 2.4 mg on liver tissue (histology) compared to placebo on top of standard of care for the first 800 randomised people at 72 weeks. Â
The trial met its primary endpoints in showing the significant and superior degree of improvement in liver fibrosis without worsening steatohepatitis with semaglutide 2.4 mg compared to placebo, as well as resolution of steatohepatitis without worsened liver fibrosis.
Week 72 data shows that for those treated with semaglutide 2.4 mg, 37.0% achieved an improvement in liver fibrosis without any deterioration in steatohepatitis in contrast to 22.5% for placebo.
During the study, 62.9% of individuals on semaglutide 2.4 mg resolved the condition of steatohepatitis without aggravating liver fibrosis, while 34.1% of individuals on placebo did the same.Â
Throughout the research, confirming previous trials regarding semaglutide 2.4mg, semaglutide 2.4mg was found to be safe and well tolerated. “The results from the ESSENCE clinical trial are very encouraging. Semaglutide will be valuable for the patients suffering from MASH,” commented Martin Holst Lange, executive vice president and head of Development at Novo Nordisk.
Among overweight and obese individuals, one in 3 suffers from MASH. This has an adverse effect on their health and is a huge area of concern. Novo Nordisk anticipates filing for US and EU regulatory clearances in the first half of 2025. Advanced findings from ESSENCE will be made at a scientific meeting set for 2024. Completion date of Part 2 of the ESSENCE Trial is in 2029.Â
The ESSENCE study assesses the effectiveness of subcutaneous semaglutide 2.4mg once a week in patients with metabolic dysfunction-associated steatohepatitis with liver fibrosis stage 2 or 3.
The ESSENCE is a two-part trial in which 1200 enrolled participants were randomized in a ratio of 2:1 receiving semaglutide 2.4 mg and placebo inclusive of soc for 240 weeks.
In part 1, this aimed to show that semaglutide 2.4 mg treatment at 72 weeks improves liver histology as assessed by liver biopsy of the first 800 randomised patients.
Part 2, aims to show in adults with MASH including patients with moderate to advanced liver fibrosis following treatment of semaglutide 2.4mg that it is associated with a lower risk of liver-related clinical events compared to placebo at 240 weeks.Â
Reference: Semaglutide 2.4 mg demonstrates superior improvement in both liver fibrosis and MASH resolution in the ESSENCE trial, https://ml-eu.globenewswire.com/Resource/Download/395f870c-3f29-49e2-a8f5-b469ae261625. Â
