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

“Lasmiditan was negative in adequately designed and conducted in vitro (bacterial reverse mutation, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.”

“Lasmiditan was not carcinogenic in 2-year rat or 6-month Tg rasH2 mouse studies.”

“Oral administration of lasmiditan (0, 50, 75, or 115 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in malformations (skeletal and visceral), increases in skeletal variations and embryofetal mortality, and decreased fetal body weight were observed at the highest dose tested, which was associated with maternal toxicity.”

“In hERG assays, IC50s for lasmiditan (~3.0 µM) and metabolites M8 and M18 (>30 µM) exceeded 4-fold the plasma Cmax in humans following oral administration of 200 mg. ECG, respiratory, and vasoactivity assessments were negative.”

“Lasmiditan was negative in adequately designed and conducted in vitro (bacterial reverse mutation, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.”

“Lasmiditan was negative in adequately designed and conducted in vitro (bacterial reverse mutation, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.”

“Lasmiditan was negative in adequately designed and conducted in vitro (bacterial reverse mutation, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.”

“Both studies were adequately conducted, and no drug-related neoplasms were identified in either species (see Executive CAC minutes, dated June 20, 2019).”

“A 26-week study in transgenic RasH2 mice and a 2-year study in Sprague-Dawley rats were conducted.”

“In hERG assays, IC50s for lasmiditan (~3.0 µM) and metabolites M8 and M18 (>30 µM) exceeded 4-fold the plasma Cmax in humans following oral administration of 200 mg. ECG, respiratory, and vasoactivity assessments were negative.”