Elafibranor (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- IQIRVO
Indications and Usage
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) [see Clinical Studies (14)]. 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).
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Myalgia, Myopathy, and Rhabdomyolysis [see Warnings and Precautions (5.1)] Fractures [see Warnings and Precautions (5.2)] Drug-Induced Liver Injury [see Warnings and Precautions (5.4)] Hypersensitivity Reactions [see Warnings and Precautions (5.5)]
Mechanism of Action
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 (EC50 = 46 nM and 14 nM, respectively, and Emax = 56% and 61%, respectively, relative to reference agonists). The potency of elafibranor and GFT1007 for PPAR-alpha activation exceeded the respective potencies for PPAR-gamma and PPAR-delta activation by approximately 3- to 8-fold. Although the in vitro pharmacology studies detected PPAR-gamma activation by elafibranor and its metabolite GFT1007, toxicology studies in rats and monkeys (species with plasma metabolite profiles comparable to human) showed none of the adverse effects that are associated with PPAR-gamma activation.