Xenleta: which tox species, and why?

“Lefamulin was evaluated in 4-week oral toxicology studies in rats and cynomolgus monkeys.”

“The major human lefamulin metabolite, BC-8041 (2R-hydroxy-lefamulin), is present in rat and monkey, the species used in the pivotal toxicology studies.”

“In a 13-week repeated dose toxicity study in monkeys, a formulation containing 6.67 mg/mL lefamulin dissolved in 10 mM citrate-buffered saline was tolerated for approximately 6 weeks”

“In repeat dose studies in both rats and monkeys, local intolerance was dose limiting by both oral and IV routes of administration.”

“Fertility, embryo-foetal development, pre- and post-natal development and juvenile toxicity studies were conducted in rats, and embryo-foetal development has been assessed in rabbits.”

“No carcinogenicity studies have been carried out, as the expected clinical use is of short duration.”

“In rats, local intolerance was not observed with a formulation containing 1.875 mg/mL lefamulin dissolved in 10 mM citrate-buffered saline when injected every 12 hours for 13 weeks.”