FDA, Health Canada reviewing semaglutide for liver disease MASH
Formulation, dosage already approved to help with weight loss
The U.S. Food and Drug Administration and Health Canada are reviewing Novo Nordisk‘s requests to approve semaglutide’s under-the-skin formulation, at a dose of 2.4 mg, for treating metabolic dysfunction-associated steatohepatitis (MASH), a serious form of fatty liver disease.
The formulation and dosage are approved in the U.S. as Wegovy for treating obese or overweight adults with cardiovascular disease, people 12 years and older with obesity, and certain overweight adults. In Canada, it’s sold as Wegovy for obese adults with cardiovascular disease.
Results from ESSENCE (NCT04822181), an ongoing global Phase 3 clinical trial showed subcutaneous semaglutide, given at 2.4 mg once weekly, promoted MASH resolution.
“Based on these data, we look forward to working with regulatory authorities to bring this potential new treatment option to patients,” Anna Windle, PhD, senior vice president of clinical development, medical and regulatory affairs at Novo Nordisk, said in a company press release.
Both health authorities gave the applications priority review, meaning decisions should be available in about six months, instead of the standard 10 months.
“Semaglutide 2.4 mg represents a therapeutic advancement for patients living with MASH, addressing a critical unmet medical need,” Vince Lamanna, president of Novo Nordisk Canada, said in a separate company press release. “Health Canada’s acceptance of the Semaglutide 2.4 mg submission for review brings us one step closer to providing the first treatment option for eligible people living with MASH.”
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously called nonalcoholic fatty liver disease, is marked by a buildup of liver fat in people who have metabolic issues like diabetes or obesity. In severe cases, MASLD can progress to MASH, where liver inflammation and scarring (fibrosis) can impair liver function. According to Novo Nordisk, about 5.2% of Canadians have MASH and that percentage is expected to increase to 6.5% by 2030.
Semaglutide mimics the activity of glucagon-like peptide-1 (GLP-1), a hormone that normally helps control blood sugar and appetite.
Results of ESSENCE study
ESSENCE enrolled nearly 1,200 adults with MASH and moderate to advanced liver fibrosis. The participants were randomly assigned to either 2.4 mg of semaglutide or a placebo, in addition to standard care, for about 4.5 years.
Results from its first part, which covered up to 72 weeks, or about 1.5 years, were published in The New England Journal of Medicine, in a study titled “Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis.” The work was funded by Novo Nordisk.
Nearly two-thirds (62.9%) of patients given semaglutide, but only about a third (34.3%) of those on a placebo, saw MASH resolution without fibrosis worsening.
The proportion of patients who had less fibrosis without MASH worsening was also significantly higher in the semaglutide group (36.8% vs. 22.4%), as was the proportion of patients who had both MASH resolution and fibrosis reduction (32.7% vs. 16.1%).
Those given semaglutide also lost significantly more weight (10.5% vs. 2%) and showed a reduction in liver damage, inflammation, and metabolic markers. Measures of bodily pain were similar in both groups.
“The results from this landmark study across 37 countries provide strong evidence that semaglutide can help patients with MASH by not only improving liver health, but also addressing the underlying metabolic issues that contribute to the disease,” Arun Sanyal, MD, the study’s co-first author at Virginia Commonwealth University, said in a university news story. “If approved, [semaglutide] could offer an additional therapeutic option for patients with MASH and fibrosis. This is crucial, given the strong link between MASH and cardiovascular, metabolic, and [kidney] conditions, where semaglutide has already shown established health benefits.”
The most common adverse events reported with semaglutide were nausea, diarrhea, constipation, and vomiting.
ESSENCE’s ongoing second part will investigate semaglutide’s effects on liver complications relative to a placebo after about 4.5 years. The study is set to end by 2029.
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