Elafibranor

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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). IQIRVO is a peroxisome proliferator-activated receptor (PPAR) agonist indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.

Elafibranor and its main active metabolite GFT1007 are peroxisome proliferator-activated receptor (PPAR) agonists, both of which activate PPAR-alpha, PPAR-gamma, and PPAR-delta in vitro. However, the mechanism by which elafibranor exerts its therapeutic effects in patients with PBC is not well understood. Pharmacological activity that is potentially relevant to therapeutic effects includes inhibition of bile acid synthesis through activation of PPAR-alpha and PPAR-delta. The signaling pathway for PPAR-delta was reported to include Fibroblast Growth Factor 21 (FGF21)-dependent downregulation of CYP7A1, the key enzyme for the synthesis of bile acids from cholesterol. An in vitro PPAR functional assay showed that both elafibranor and GFT1007 produced activation of PPAR-alpha (EC 50 = 46 nM and 14 nM, respectively, and E max = 56% and 61%, respectively, relative to reference agonists).

Before treatment, evaluate for muscle pain or myopathy, and/or verify that females of reproductive potential are not pregnant. The recommended dosage is 80 mg orally once daily with or without food.

None. None.

Myalgia, Myopathy, and Rhabdomyolysis: Assess for muscle pain and myopathy prior to IQIRVO initiation. Consider periodic assessment (clinical exam, CPK measurement). Interrupt IQIRVO if there is new onset or worsening of muscle injury, or muscle pain. Fractures: The risk of fracture should be considered in the care of patients treated with IQIRVO. Apply current standards of care for assessing and maintaining bone health. Adverse Effects on Fetal and Newborn Development: May cause fetal harm. Verify that a female of reproductive potential is not pregnant prior to initiating IQIRVO. Advise females of reproductive potential to avoid use of hormonal contraceptives containing ethinyl estradiol and to use alternative contraception. Drug-Induced Liver Injury: Obtain clinical and laboratory assessments at treatment initiation and monitor thereafter according to routine patient management.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myalgia, Myopathy, and Rhabdomyolysis Fractures Drug-Induced Liver Injury Hypersensitivity Reactions Most common adverse reactions with IQIRVO (reported in ≥ 5% and higher compared to placebo) are weight gain, diarrhea, abdominal pain, nausea, vomiting, arthralgia, constipation, muscle injury, fracture, gastroesophageal reflux disease, dry mouth, weight loss, and rash.

Hormonal Contraceptives: Switch to progestin only products containing levonorgestrel/norgestrel, intrauterine systems, or effective non-hormonal contraceptives during treatment and for at least 3 weeks after last dose. HMG-CoA Reductase Inhibitors: Monitor for signs and symptoms of muscle injury. Strong CYP2C8 Inhibitors: Avoid concomitant use with strong CYP2C8 inhibitors (e.g. gemfibrozil). If concomitant use cannot be avoided, monitor patients for adverse reactions. Other Peroxisome Proliferator-Activated Receptor-Alpha (PPAR-alpha) Agonists: Monitor for signs and symptoms of liver injury and muscle injury. Other PPAR-gamma Agonists: Monitor for signs and symptoms of liver injury. Rifampin: Monitor the biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during IQIRVO treatment.

Store at room temperature 15°C to 30°C (59°F to 86° F). Store in the original package (bottle and carton) to protect from moisture and light.