Nonalcoholic steatohepatitis (NASH) management is a situation which still needs to be answered. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that affects important inflammatory, metabolic, and fibrogenic processes in NASH development. The percentage of patients who experienced a drop of at least 2 points in the SAF-A score without worsening of fibrosis in this phase 2b study including patients with active NASH was substantially greater with the 1200-mg dosage of lanifibranor than with placebo.
This study was conducted by Sven M. Francque and team, the findings are published in The New England Journal of Medicine on 21st October, 2021.
Patients with noncirrhotic, highly active NASH were randomly allocated in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks in this phase 2b, double-blind, randomized, placebo-controlled study. The primary end point was a decrease of at least 2 points in the SAF-A score (the activity component of the Steatosis, Activity, Fibrosis [SAF] scoring system, which includes ballooning and inflammation scores) without worsening of fibrosis; SAF-A scores range from 0 to 4, with higher scores indicating more severe disease activity. Secondary endpoints were NASH resolution and fibrosis regression.
A total of 247 individuals were randomly assigned, with 103 (42%) having type 2 diabetes mellitus and 188 (76%) having considerable (moderate) or advanced fibrosis. The percentage of patients who had a drop of at least 2 points in the SAF-A score without worsening of fibrosis was substantially greater in those who got the 1200-mg dosage of lanifibranor, but not in those who received the 800-mg dose, than in those who received placebo. The results indicated lanifibranor dosages of 1200-mg and 800-mg over placebo for resolution of NASH without worsening of fibrosis, improvement in fibrosis stage of at least 1 without worsening of NASH, and resolution of NASH with improvement in fibrosis stage of at least 1.
The lanifibranor groups had lower levels of liver enzymes and higher levels of the majority of lipid, inflammatory, and fibrosis indicators. The dropout rate for adverse events was less than 5% and was consistent across study groups. Lanifibranor caused increased diarrhea, nausea, peripheral edema, anemia, and weight gain than placebo.
In conclusion, the favorable results of this study justify continued evaluation of lanifibranor in phase 3 studies.
Reference:
Francque, S. M., Bedossa, P., Ratziu, V., Anstee, Q. M., Bugianesi, E., Sanyal, A. J., Loomba, R., Harrison, S. A., Balabanska, R., Mateva, L., Lanthier, N., Alkhouri, N., Moreno, C., Schattenberg, J. M., Stefanova-Petrova, D., Vonghia, L., Rouzier, R., Guillaume, M., Hodge, A., … Abdelmalek, M. F. (2021). A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. In New England Journal of Medicine (Vol. 385, Issue 17, pp. 1547–1558). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2036205