Elafibranor Outperforms Placebo in Improving Biochemical Indicators of Cholestasis: NEJM
Patients with primary biliary cholangitis who don't respond to standard therapy have a high risk of cirrhosis and poor quality of life. Previous studies have demonstrated the effect of Elafibranor in this rare chronic liver disease. It reduced alkaline phosphatase levels, a disease activity marker.
A recent study published in the New England Journal of Medicine has concluded that management with elafibranor causes more significant improvements in relevant biochemical indicators of cholestasis when compared to placebo.
It is already known that Primary biliary cholangitis is a rare, chronic cholestatic liver disease. It is related to the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. There needs to be more data available on whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, is beneficial in its treatment. This background was investigated in the present study.
In this phase 3 trial, researchers administered elafibranor or a placebo to patients with primary biliary cholangitis who had an inadequate response to or unacceptable side effects with ursodeoxycholic acid. They randomly assigned patients in a 2:1 ratio to receive once-daily elafibranor at an 80 mg or placebo dose. The primary goal was a biochemical response (alkaline phosphatase levels) by week 52. They also measured pruritus intensity and using the Worst Itch Numeric Rating Scale.
Key findings from the study are:
- One hundred sixty-one patients underwent randomization.
- A biochemical response was observed in 51% of the patients (55/108) who received elafibranor and 4% (2/53) who received placebo.
- There was a difference of 47 percentage points.
- At week 52, The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group, with a difference of 15 percentage points.
- Among patients (44 patients in the elafibranor group and 22 in the placebo group) who had moderate-to-severe pruritus, the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (−1.93 vs. −1.15; difference, −0.78).
- Abdominal pain, diarrhoea, nausea, and vomiting were the adverse events more frequent with elafibranor than with placebo.
They said, "In our study, we found that elafibranor significantly improves relevant biochemical indicators of cholestasis."
As acknowledged, the study was funded by GENFIT and Ipsen.
Reference:
Kowdley et al. Efficacy and safety of elafibranor in primary biliary cholangitis. The New England Journal of Medicine. https://doi.org/10.1056/nejmoa2306185
