A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
New England Journal of Medicine — Francque SM, Bedossa P, Ratziu V, et al. | October 25, 2021
In view of the benefit conferred by 1,200-mg dose of lanifibranor (a pan-peroxisome proliferator–activated receptor agonist) vs placebo in active nonalcoholic steatohepatitis (NASH) patients in this trial, further evaluation of lanifibranor in phase 3 trials is supported.
This phase 2b, double-blind, randomized, placebo-controlled trial comprised 247 patients with noncirrhotic, highly active NASH randomized to receive 1,200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks.
Treatment with 1,200-mg dose of lanifibranor vs placebo conferred reduction of at least 2 points in the SAF-A score (the activity part of the Steatosis, Activity, Fibrosis scoring system that includes scores for ballooning and inflammation), without worsening of fibrosis, in a significantly higher percentage of patients.
Compared with placebo, both the 1,200-mg and 800-mg doses of lanifibranor were superior for resolution of NASH without worsening of fibrosis, improvement in fibrosis stage of at least 1 without worsening of NASH, and resolution of NASH plus improvement in fibrosis stage of at least 1.
The lanifibranor groups exhibited reduction in liver enzyme levels and improvement in the levels of the majority of lipid, inflammatory, and fibrosis biomarkers.
For adverse events, the dropout rate was less than 5% and was similar across the trial groups.
Lanifibranor, vs placebo, was more frequently associated with diarrhea, nausea, peripheral edema, anemia, and weight gain.