FDA approved Iqirvo (elafibranor) for Primary Biliary CholangitisFDA approved new drug Iqirvo for a rare liver disease.

Iqirvo is a peroxisome proliferator-activated receptor (PPAR) agonist. The exact mechanism by which it exerts its therapeutic effect in PBC is not fully described in the label.

Iqirvo is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Use is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

The recommended dosage is 80 mg taken orally once daily with or without food. Before initiating treatment, evaluate for muscle pain or myopathy, and verify that females of reproductive potential are not pregnant. Administer Iqirvo at least 4 hours before or 4 hours after administering a bile acid sequestrant, or at as great an interval as possible.

Efficacy was evaluated in Study 1 (NCT04526665), a multi-center, randomized, double-blind, placebo-controlled study in 161 adults with PBC with inadequate response or intolerance to UDCA. Patients were randomized to Iqirvo 80 mg (n=108) or placebo (n=53) once daily for at least 52 weeks. The primary endpoint was biochemical response at Week 52, defined as achieving ALP <1.67 times ULN, total bilirubin (TB) ≤ ULN, and ALP decrease ≥15% from baseline. ALP normalization (ALP ≤ ULN) was a key secondary endpoint. Iqirvo demonstrated greater improvement on biochemical response and ALP normalization at Week 52 compared to placebo. The study population was predominantly female (96%) and White (91%), with a mean age of 57 years. Most patients (95%) received study treatment in combination with UDCA.

Use of Iqirvo is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). The label includes warnings regarding muscle-related adverse events (evaluate for muscle pain or myopathy before initiating) and pregnancy (verify that females of reproductive potential are not pregnant prior to initiation). No contraindications are listed in the provided label text.

Iqirvo provides a new treatment option for adults with PBC who have an inadequate response to UDCA or are unable to tolerate UDCA. It is used in combination with UDCA when tolerated, or as monotherapy. Approval is based on a surrogate endpoint (ALP reduction) under accelerated approval; clinical benefit on survival or liver decompensation has not been established. It should not be used in patients with decompensated cirrhosis.