Lanifibranor meets efficacy, safety endpoints in phase 2b NASH trial

Inventiva announced lanifibranor met primary and secondary endpoints in a phase 2b study for treatment of nonalcoholic steatohepatitis, according to speaker at an Inventiva web conference.

“Lanifibranor (1,200 mg) met the primary endpoints with a statistically significant reduction, after 6 months of treatment, of the Steatosis Activity Fibrosis score, which combines assessments of hepatocellular inflammation and ballooning, with no worsening in intention to treat and per protocol populations,” Pierre Broqua, PhD, chief scientific officer and cofounder of Inventiva, said during his presentation.

The NATIVE trial (NAsh Trial to Validate IVA337 Efficacy) comprised patients from 71 sites around the world; 247 in an intention-to-treat (ITT) cohort and 194 in a per protocol (PP) cohort.

In the ITT arm, investigators randomly assigned patients to receive 800 mg (n = 83) of lanifibranor, 1,200 mg (n = 83) or placebo (n = 81). Broqua reported the 24-week assessment was completed by 77 patients in the 800 mg arm, 77 in the 1,200 mg arm and 74 in the placebo arm.

Researchers randomly assigned patients in the PP cohort based on paired biopsies (63 to 800 mg, 69 to 1,200 mg, and 62 to placebo). They reported no deviations impacted the efficacy results.

Trial data showed 49% of patients in the ITT arm and 55% in the PP arm who received the 1,200 mg dose saw a 2-point reduction in their combined score of inflammation and ballooning with no worsening of fibrosis.

Broqua reported that secondary endpoints, which included NASH resolution with no worsening of fibrosis and improvement of liver fibrosis with no worsening of NASH in both ITT and PP populations, were met by all patients who received lanifibranor.

He also said lanifibranor improved fibrosis by at least one stage without worsening NASH, with a highly significant impact seen with 1,200 mg in both the ITT and PP cohorts. After 6 months of treatments, results from the ITT arm showed 33% of patients who received 800 mg and 45% who received 1,200 mg achieved resolution of NASH with no worsening of fibrosis. In the PP arm, 40% of patients who received 800 mg of lanifibranor and 49% who received 1200 mg met the study end point.

“Lanifibranor continued to show a favorable safety and tolerability profile and these positive top line results support Inventiva’s decision to move forward with the clinical development of lanifibranor and enter into pivotal phase 3 development,” Broqua said. “Lanifibranor is the first drug candidate to achieve statistically significant effects on the FDA and [European Medicines Agencies (EMA)] primary endpoints relevant for seeking accelerated approval [including] NASH resolution with no worsening of fibrosis and improvement of fibrosis with no worsening of NASH.”