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

MASH, formerly known as nonalcoholic steatohepatitis (NASH), is the advanced form of metabolic dysfunction-associated fatty liver disease (MAFLD).MASH is the leading cause of liver-related mortality, imposing an increasingly heavy burden on global health systems.In addition, MASH patients, especially those with more metabolic risk factors (hypertension, comorbid type 2 diabetes), face an increased risk of cardiovascular adverse events, along with correspondingly higher morbidity and mortality.Once MASH progresses to significant liver fibrosis (stages F2 and F3), the risk of patients developing adverse liver damage outcomes increases sharply. According to statistics,There are over 250 million MASH patients globally, and the number of advanced-stage patients is expected to double by 2030.Studies show that among overweight or obese populations, more than one-third of individuals simultaneously suffer from MASH.MASH patients typically exhibit no or only mild symptoms in the early stages of the disease, often leading to delayed diagnosis.Compared with 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 participants randomly assigned in a 2:1 ratio to receive either Wegovy or placebo 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, compared to placebo, can reduce moderate toSevereRisk of Liver-Related Clinical Events in Adult MASH Patients with Hepatic Fibrosis.

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Analysis of the first part of the trial showed that the trial met its primary endpoint, meaning that compared with placebo, Wegovy improved liver fibrosis without worsening nonalcoholic steatohepatitis (NASH), and achieved the regression of NASH without exacerbating liver fibrosis.At week 72, 37.0% of patients in the Wegovy group achieved improvement in liver fibrosis without worsening of steatohepatitis, compared to 22.5% in the placebo group. Additionally, 62.9% of patients in the Wegovy group achieved steatohepatitis resolution without worsening of liver fibrosis, compared to 34.1% in the placebo group.

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

Semaglutide is aGlucagon-Like Peptide-1 (GLP-1)Receptor agonist, which can stimulate insulin production, inhibit glucagon secretion, reduce appetite and food intake.Semaglutide was initially developed as a treatment for type 2 diabetes.ApprovedLaunched (brand name: Ozempic), in view of its significant effect on weight loss, the FDA in June 2021ApprovalIt is used to treat ordinary obese patients (trade name: Wegovy),It isThe first new drug approved by the U.S. FDA for controlling common obesity or overweight since 2014.The drugAnd later that same year, it received EU approval for the treatment of obesity indications.。In March this year, the US FDAApprovalWegovy Injection Reduces Risk of Cardiovascular Death, Heart Attack, and Stroke in Adults with Cardiovascular Disease and Obesity or Overweight.

The successful development of Semaglutide inIn recent years, it has received widespread attention from the industry. In addition to treating diabetes and obesity, the drug has also shown potential in treating various other indications.Last month, an article was published in a well-known journalAlzheimer's & DementiaTheThe study pointed out, compared with other diabetes medications,Semaglutide Treatment Associated with 40%-70% Reduced Risk of Alzheimer's Disease (AD) Diagnosis in Patients with Type 2 Diabetes.This discovery supportsSemaglutideFurther research in neurodegenerative diseases. In the same month,Results from the STEP9 Phase 3 clinical trial showed that in patients with obesity-related knee osteoarthritis accompanied by moderate to severe pain, treatment with semaglutide significantly reduced knee osteoarthritis pain scores.PublishIn The New England Journal of Medicine (NEJM）。And this SeptemberAnnounced at the European Academy of Dermatology and Venereology (EADV) CongressGroundbreaking ResearchThis indicates that,AcceptSemaglutide-treated obese patients with chronic skin disease hidradenitis suppurativa (HS)The frequency of HS attacks decreased, with the average frequency dropping from once every 8.5 weeks to once every 12 weeks.In addition,The well-known medical journal The Lancet also released Wegovy in August this year.Post-hoc AnalysisResults. The analysis shows,In patients with heart failure with preserved ejection fraction (HFpEF), Wegovy reduced the risk of the composite endpoint of cardiovascular death or worsening heart failure events by 31%.These data support the use of Wegovy as an effective treatment to reduce the risk of clinical heart failure events in patients with HFpEF, for whom current treatment options are relatively limited.

ExpectationsThe potential of semaglutide for other indications can be further confirmed and approved by regulators as soon as possible, to benefit a wide range of patients.

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References:

[1] 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

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