How effective is Elafibranor-Iqirvo?

Primary cholangitis (PBC) is a rare chronic cholestatic liver disease characterized by destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether Elafibranor-Iqirvo, an oral dual peroxisome proliferator-activated receptor (PPAR) alpha and delta agonist, is beneficial as a treatment for primary biliary cholangitis is unclear.

In a controlled trial of Iqirvo versus placebo, patients with primary cholangitis who had failed to respond to ursodeoxycholic acid (UDCA) or had unacceptable side effects were randomly assigned (2:1) to receive a once-daily dose of Iqirvo 80 mg or placebo. The primary endpoint was biochemical response at week 52 (defined as alkaline phosphatase level <1.67 times the upper limit of normal range, a ≥15% decrease from baseline, and normal total bilirubin level). Key secondary endpoints were normalization of alkaline phosphatase levels at Week 52 and change from baseline to Weeks 52 and 24 in itch intensity as measured by the Worst Itch Numerical Rating Scale (Worst score from 0 [not itchy] to 10 [worst itch imaginable]).

Clinical study results showed that 51% of patients treated with Iqirvo and 4% of patients treated with placebo experienced a biochemical response (primary endpoint), with a difference of 47 percentage points (95% confidence interval [CI] of 32-57; P <0.001). At Week 52, 15% of patients in the Iqirvo group and no patients in the placebo group had normalized alkaline phosphatase levels (difference, 15 percentage points; 95% CI, 6-23; P=0.002). Among patients with moderate to severe pruritus (44 in the Iqirvo group and 22 in the placebo group), the least squares mean change in WI-NRS from baseline to week 52 was not significantly different between the two groups. The incidence of adverse events, including abdominal pain, diarrhea, nausea and vomiting, was higher in the Iqirvo group compared with the placebo group.

In summary, Iqirvo treatment improved biochemical markers of cholestasis compared with placebo.