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

“Trofinetide was negative in in vitro (bacterial reverse mutation, chromosomal aberration in Chinese hamster ovary cells) and in vivo (mouse micronucleus) assays.”

“The nonclinical data submitted to the NDA support approval of trofinetide for the proposed indication, with appropriate labeling and post-marketing requirements for carcinogenicity studies in mouse and rat.”

“Embryofetal development studies were conducted in rat and rabbit. Trofinetide was administered orally during the period of organogenesis at doses of 0, 150, 450, and 1000 mg/kg BID (0, 300, 900, and 2000 mg/kg/day) to rats and at doses of 0, 75, 150, and 300 mg/kg BID (0, 150, 300, and 600 mg/kg/day) to rabbits. No adverse effects on embryofetal development were observed in either species.”

“In dogs, IV infusion of trofinetide (800 mg/kg) had no effects on heart rate or arterial blood pressure; however, the QTcV interval was slightly prolonged by 19 to 33 ms at ≥ 400 mg/kg. The IC50 value of trofinetide on hERG currents was estimated at ≥ 20 mM.”