Iqirvo: genotox, carcinogenicity and repro: done or skipped?

“Elafibranor was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vivo rat micronucleus assay, and the in vivo comet assay in rats. Elafibranor was positive for mutagenicity in L5178Y tk+/- mouse lymphoma cells.”

“The liver tumors in mice and rats may be attributed to the expected rodent-specific PPARα-related liver toxicity and its related consequences. Therefore, the relevance to humans is uncertain.”

“Treatment of pregnant rats with elafibranor during organogenesis through lactation resulted in stillbirths, reduced survival, decrease in pup body weight, and/or blue/black discoloration of the caudal section of body, which occurred at maternal plasma drug exposures lower than or approximately equal to human exposure at the recommended dose”

“A single dose oral administration of elafibranor at 30 mg/kg had no effect on heart rate, arterial blood pressure, or electrocardiogram (Leads I, II, III, aVL, aVR and aVF) in the in vivo telemetry study in conscious dogs. At the doses of 100, 300, and 1000 mg/kg, elafibranor induced delayed (in terms of duration) and dose-dependent tachycardia.”