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

“Genetic toxicology studies showed that seladelpar was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma assay, and the in vivo mouse micronucleus test.”

“In a 2-year study in mice, oral administration of seladelpar produced hepatocellular adenoma or carcinoma at 6 times the human exposure (AUC at the recommended dose) in males and at 140 times the human exposure in females.”

“Seladelpar had no effects on fertility or reproductive function in male rats at up to 271 times the human exposure (AUC) at the recommended dose or in female rats at up to 115 times the human exposure.”

“Overall, the safety pharmacology data indicates that there are no safety issues of significant concern for cardiovascular function, respiratory function, or the central nervous system.”

“Seladelpar was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma assay, and the in vivo mouse micronucleus test.”

“Seladelpar was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma assay, and the in vivo mouse micronucleus test.”

“Seladelpar was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma assay, and the in vivo mouse micronucleus test.”

“Carcinogenicity studies were performed in rats and mice. In a 2-year study in mice, oral administration of seladelpar produced hepatocellular adenoma or carcinoma at 6 times the human exposure (AUC at the recommended dose) in males and at 140 times the human exposure in females.”

“The carcinogenicity of seladelpar was evaluated in 2-year studies in mice and rats”

“The inhibition of hERG was assessed for seladelpar up 3 μM showing an inhibition of 7.7%. The margin based on the free drug concentration of 3.5 nM in human, is x857.”