What it is
Efinopegdutide is a once-weekly co-agonist of the GLP-1 and glucagon receptors, with a relative receptor potency balance of about 2:1, in development for metabolic dysfunction-associated steatohepatitis (MASH), the inflammatory form of fatty liver disease. In this phase 2b, randomised, placebo-controlled, double-blind study at 176 centres in 26 countries, adults with biopsy-confirmed MASH and stage 2 or 3 fibrosis were assigned to efinopegdutide at 4 mg, 7 mg or 10 mg, placebo, or open-label semaglutide 2.4 mg, all injected once a week; 381 participants received at least one dose. At week 52, MASH resolved without worsening of fibrosis in 56%, 63% and 61% of those analysed on the three doses, against 13% on placebo and 53% on semaglutide. Fibrosis improved by at least one stage without worsening of steatohepatitis in 43%, 52% and 34% on the three doses against 21% on placebo (differences from placebo with p=0.0038 at 4 mg and p<0.0001 at 7 mg; at 10 mg p=0.072, with a confidence interval that included no difference), and in 25% on semaglutide. Gastrointestinal events were the most frequent adverse events with efinopegdutide, highest at 10 mg, where 11% stopped treatment because of adverse events, against 3-4% at the other doses and 1% on placebo.
Why it matters
MASH resolved more often than on placebo at every dose after a year, and the authors single out 7 mg, which also improved fibrosis in about half of the patients on it. At that dose the difference from placebo was 49.5 percentage points for MASH resolution and 30.4 percentage points for fibrosis improvement, and the authors judge it to have the most favourable balance of benefit and risk. The abstract does not give their reasoning; it reports that 10 mg had the most discontinuations for adverse events (11%) and the smallest fibrosis gain over placebo (34% against 21%). The study also gave semaglutide openly to one group, and the abstract reports its rates without a statistical comparison with efinopegdutide. The authors conclude that the findings support efinopegdutide's potential as a once-weekly treatment for MASH.
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Filed underLiver Disease Diagnosis and Treatment, Diabetes Treatment and Management, Hepatitis C virus research
