Over 60% of patients with fatty liver inflammation have seen regression! Semaglutide demonstrates potential in treating MASH

Novo Nordisk announced today the primary results of the ongoing ESSENCE pivotal Phase 3 trial Part 1. The analysis showed that its developed weight loss therapy Wegovy (semaglutide) significantly alleviates liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASH) compared to placebo and achieves resolution of steatohepatitis. Novo Nordisk expects to submit a regulatory application for Wegovy for the treatment of MASH to the U.S. and EU regulatory authorities in the first half of 2025. Detailed data from ESSENCE will be presented at an upcoming scientific conference. Part 2 of the trial will continue, with results expected in 2029.

MASH, formerly known as non-alcoholic steatohepatitis (NASH), is an advanced form of metabolic dysfunction-associated fatty liver disease (MAFLD). MASH is a leading cause of liver-related mortality and poses an increasing burden on global health systems. Additionally, MASH patients, particularly those with more metabolic risk factors (hypertension, comorbid type 2 diabetes), have an increased risk of cardiovascular adverse events, with corresponding increases in morbidity and mortality. Once MASH progresses to significant liver fibrosis (F2 and F3 stages), the risk of adverse liver outcomes for patients sharply rises. It is estimated that there are over 250 million MASH patients globally, and the number of advanced patients is expected to double by 2030. Research shows that more than one-third of overweight or obese individuals also have MASH. MASH patients often have subtle or even no obvious symptoms in the early stages of the disease, which often leads to delayed diagnosis. Compared to the general population, MASH patients have a higher risk of progressing to advanced liver disease (including liver cancer).

ESSENCE is a Phase 3 trial designed to evaluate the efficacy and safety of once-weekly Wegovy (subcutaneous injection of 2.4 mg semaglutide) compared to placebo in adult patients with MASH and moderate to severe liver fibrosis (stage 2 or 3). The ESSENCE trial is divided into two parts, with 1,200 subjects randomly assigned in a 2:1 ratio to receive Wegovy or placebo treatment for up to 240 weeks, while also receiving standard treatment for MASH. Part 1 of the trial aims to assess whether Wegovy improves liver histological outcomes in MASH patients based on biopsy samples from the first 800 randomized patients at week 72. Part 2 of the trial aims to evaluate whether Wegovy reduces the risk of liver-related clinical events in adult MASH patients with moderate to severe liver fibrosis compared to placebo at week 240.

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The analysis of Part 1 of the trial showed that the trial achieved its primary endpoint. That is, compared to the placebo, Wegovy improved liver fibrosis without worsening steatohepatitis, and achieved the resolution of steatohepatitis without worsening liver fibrosis. At week 72, 37.0% of patients in the Wegovy group achieved improvement in liver fibrosis without worsening steatohepatitis, while the proportion in the placebo group was 22.5%. 62.9% of patients in the Wegovy group achieved resolution of steatohepatitis without worsening liver fibrosis, while the proportion in the placebo group was 34.1%.

In the trial, the safety and tolerability results of Wegovy were consistent with previous trials.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that stimulates insulin production, inhibits glucagon secretion, and reduces appetite and food intake. Semaglutide was initially approved for the treatment of type 2 diabetes (brand name: Ozempic), and due to its significant effects on weight loss, the FDA approved it for the treatment of general obesity in June 2021 (brand name: Wegovy). It is the first new drug approved by the U.S. FDA since 2014 for the control of general obesity or overweight. The drug was also later approved by the European Union for the treatment of obesity indications. In March of this year, the U.S. FDA approved Wegovy injection for reducing the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and obesity or overweight.

The successful development of semaglutide has garnered widespread attention in the industry in recent years. In addition to treating diabetes and obesity, the drug has also shown potential for treating other different indications. Last month, a study published in the renowned journal Alzheimer's & Dementia indicated that, compared to other diabetes medications, semaglutide treatment was associated with a 40%-70% reduced risk of Alzheimer's disease (AD) diagnosis in patients with type 2 diabetes. This finding supports further research on semaglutide in neurodegenerative diseases. In the same month, results from the STEP9 Phase 3 clinical trial showed that in patients with obesity-related knee osteoarthritis with moderate to severe pain, semaglutide treatment significantly reduced the patients' knee osteoarthritis pain scores, with the results published in the New England Journal of Medicine (NEJM). Additionally, a groundbreaking study presented at the European Academy of Dermatology and Venereology (EADV) conference in September this year indicated that obese patients with chronic skin disease hidradenitis suppurativa (HS) receiving semaglutide treatment experienced a reduction in the frequency of HS flare-ups, with the average frequency decreasing from once every 8.5 weeks to once every 12 weeks. Furthermore, the prestigious medical journal The Lancet also published a post-marketing analysis of Wegovy in August this year. The analysis showed that in patients with heart failure with preserved ejection fraction (HFpEF), Wegovy reduced the risk of composite endpoints of cardiovascular death or heart failure worsening events by 31%. ** These data support the use of Wegovy as an effective treatment to reduce the risk of clinical heart failure events in HFpEF patients, for whom treatment options are currently relatively limited