2023-11-20 13:40:01
Non-alcoholic fatty liver disease (NASH) is a common chronic disease characterized by the accumulation of fat in the liver, which affects more than 200,000 people in France, according to Inserm. Reversible through lifestyle changes, this disease, which can progress to fibrosis or even cirrhosis, does not yet benefit from specific treatment targeting steatosis, inflammation and liver fibrosis. An analogue of FGF21 (fibroblast growth factor 21), a protein regulating hepatic lipid metabolism, pegozafermin has been the subject of encouraging preclinical and phase I studies. Its long duration of action allows administration once a week or once every two weeks.To more precisely determine the safety and effectiveness of pegozafermin once morest NASH, an international team of researchers conducted a clinical trial of multicenter randomized, double-blind, placebo-controlled phase II: 222 US patients with biopsy-confirmed NASH with F2/F3 fibrosis (median age 55.6 years, 61% women) were randomized to receive either placebo all weeks, either a placebo every two weeks, or 15 mg of pegozafermin once a week, or 30 mg of pegozafermin once a week, or, finally, 44 mg of pegozafermin once every two weeks. The two primary endpoints were resolution of steatosis without worsening of fibrosis and improvement of fibrosis (≥1 fibrosis stage) without worsening of NASH following 24 weeks of treatment. The results of this study have been published in September 2023 in the NEJM. Only 2% of patients in the placebo groups experienced resolution of their NASH, compared to 37% in the 15 mg group, 23% in the 30 mg group and 26% in the 44 mg group – all significant differences compared to placebo. Similarly, only 7% of patients in the placebo groups saw their fibrosis improve, compared to 22% of the 15 mg group (the only non-significant difference compared to the placebo), 26% of the 30 mg group and 27% of the 44 mg group. .The most frequent adverse events were nausea (25% of treated patients versus 9% of placebos) and diarrhea (18% of treated patients versus 6% of placebos).µIn conclusion, in this phase IIb study, the treatment with pegozafermin significantly improves NASH and hepatic fibrosis in patients with histologically proven NASH and F2/F3 fibrosis, compared to placebo. These very encouraging results justify the implementation of a phase III study.
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#Molecule #effective #NASH #liver #fibrosis
