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Elafibranor safely reduces NASH without worsening fibrosis

In a phase 2 study, elafibranor was well-tolerated and led to resolved nonalcoholic steatohepatitis without worsening fibrosis, according to published findings.  

Researchers randomly assigned 276 patients with NASH without cirrhosis to receive either 80 mg of elafibranor (GFT505, GenFit; n=93), 120 mg of elafibranor (n = 91) or placebo (n = 92) daily for 52 weeks. After treatment, liver biopsies were performed and patients were followed up 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol-defined and modified definitions, according to the research.

In addition, the different doses of elafibranor were compared with the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score (NAS).

Based on a post-hoc analysis for the modified definition, results of intention-to-treat analysis showed that more patients in the 120-mg group had resolved NASH without the worsening of fibrosis compared with patients in the placebo group (19% vs, 12%; OR = 2.31; 95% CI, 1.02–5.24). However, there was no significant difference between any of the elafibranor and placebo groups in the protocol-defined primary outcome.

In post-hoc analyses of patients with a NAS greater than 4 (n = 234), more patients who received 120 mg of elafibranor had resolved NASH compared with patients given placebo, based on both the protocol definition (20% vs. 11%; OR = 3.16; 95% CI, 1.22–8.13) and the modified definitions (19% vs. 9%; OR = 3.52; 95% CI, 1.32–9.4).

Patients with resolved NASH after receiving 120 mg of elafibranor had reduced liver fibrosis stages compared with patients who did not experience resolved NASH (P < .001).

Among patients who received 120 mg of elafibranor, liver enzymes, lipids, glucose profiles and systemic inflammation markers were lower compared with the placebo group.

Overall, elafibranor was well-tolerated, with most adverse events being mild and similar among the groups. Six patients in the placebo group discontinued treatment due to adverse events, seven in the 80-mg group and five in the 120-mg group. Elafibranor did not cause weight gain or cardiac events, but led to mild, yet reversible, increases in serum creatinine (P < .001).

The researchers concluded: “This randomized controlled trial provides evidence that pharmacological modulation of the [peroxisome proliferator activated receptor-alpha and receptor-delta] nuclear receptors results in substantial histological improvement in NASH, including resolution of steatohepatitis, and improvement of the cardiometabolic risk profile, with a favorable safety profile.” – by Melinda Stevens

Disclosure: Ratziu reports consulting for Abbott, AstraZeneca, Boehringer-Ingelheim, Galmed, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Novartis, Roche-Genentech, Sanofi Aventis-Genzyme, Takeda, Tobira and receiving research support from the European Community’s Seventh Framework Program. Please see the full study for a list of all other authors’ relevant financial disclosures.