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

“Mix-ISA247 (approximately 50: 50 cis-trans mixture) was negative for genetic toxicity in the in vitro bacteria reverse mutation assay (Ames) test, a chromosomal aberration test with CHO cells, and an in vivo micronucleus assay in rats after single oral doses up to 2000 mg/kg.”

“Two-year studies were conducted in rats and mice. In the rat study, there were no voclosporin-related neoplasms in either males or females. In the mouse study, females had a significant increase in voclosporin-related malignant lymphomas at the high dose of 30 mg/kg/day”

“Mix-ISA247 caused a decrease in litter size and numbers of viable pups and an increase in resorptions (both early and late) at 25 mg/kg/day in the embryofetal development study in rats.”

“Cardiovascular studies in conscious cynomolgus monkeys found a that voclosporin, mix-ISA247 or cis-enhance ISA247 at a high dose of 200 mg/kg increased the QTc interval. There was also a signal for QTc prolongation from the hERG assay and Purkinje fiber electrophysiology assay.”