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

“Elinzanetant showed no genotoxic potential in bacterial mutation assay (Ames test), mouse lymphoma assay, and in vivo bone marrow micronucleus test in rats.”

“In a 2-year carcinogenicity study in female rats, oral doses of elinzanetant ≥60 mg/kg/day (29-fold the total AUC(0-24) at the human therapeutic dose) increased the incidence of endometrial adenocarcinoma, the combination of malignant and benign endometrial tumors and squamous cell carcinoma of the uterus, and lymphomas of the hematolymphoid system.”

“Based on findings from animal reproduction studies, elinzanetant may cause pregnancy loss or stillbirth when administered during pregnancy. Fetal malformations were not observed in these animal studies.”

“Elinzanetant did not generate major safety signals in a complete battery of safety pharmacology studies (cardiovascular, respiratory, and CNS). Elinzanetant inhibited the activity of hERG channels with an IC50 of approximately 31μM that provides multiples of exposure of 14X and 4,820X, based on the maximum plasma concentration (Cmax) and Cmax, unbound at the maximal recommended human dose, respectively.”