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

“Avacopan was negative in all assays including the in vitro bacterial mutagenicity study (Ames test), in vitro mouse lymphoma forward-mutation assay, and in vivo rat bone marrow micronucleus study.”

“Two-year carcinogenicity studies in Sprague-Dawley rats and Syrian hamsters were conducted to assess the carcinogenic potential of avacopan. Avacopan demonstrated no tumorigenic potential in a study with rats that received oral doses up to 100 mg/kg/day (approximately 3 times the MRHD in adults on an AUC basis) and a study in hamsters that received oral doses up to 100 mg/kg/day (approximately 6 times the MRHD in adults on an AUC basis).”

“In embryofetal development studies with hamsters and rabbits, no fetal harm or malformations were observed with oral doses of CCX168 up 1000 and 200 mg/kg/day.”

“In the telemetry study in conscious monkeys, there were no effects on cardiovascular (blood pressure) and electrocardiographic parameters (P, PR, QRS, QT and QTc intervals, and R amplitude) following single oral doses up to 50 mg/kg, the highest dose tested.”

“Avacopan was not mutagenic or clastogenic in the following assays: in vitro bacterial reverse mutation (Ames) test, in vitro mouse lymphoma assay, and in vivo rat micronucleus test.”

“Avacopan was not mutagenic or clastogenic in the following assays: in vitro bacterial reverse mutation (Ames) test, in vitro mouse lymphoma assay, and in vivo rat micronucleus test.”

“Avacopan was not mutagenic or clastogenic in the following assays: in vitro bacterial reverse mutation (Ames) test, in vitro mouse lymphoma assay, and in vivo rat micronucleus test.”

“Two-year carcinogenicity studies in Sprague-Dawley rats and Syrian hamsters were conducted to assess the carcinogenic potential of avacopan.”

“The 2-year carcinogenicity studies in rat and hamster were reviewed under NDA 214487”

“In vitro, CCX168 did not inhibit hERG channel current in HEK293 cells, stably expressing hERG, at concentrations up to 6.9 µM. CCX168-M1 inhibited hERG channel currents by 38% at 3 μM.”