Xdemvy: what flexibility did regulators accept, and why?

“Based on the totality of Sponsor’s arguments, this reviewer judged the waiver request for carcinogenicity studies receivable since the weight of evidence indicated no cause for concerns in the animals or humans, nor significant systemic exposure for a long period of time that would justify evaluating the cancer risk with Lotilaner Ophthalmic Solution, 0.25%, for the indication sought.”

“Nasal turbinate and nasopharynx were not examined under the microscope in any of the ocular studies which was a drawback to the complete evaluation of the potential ocular toxicity of Lotilaner Ophthalmic Solution, 0.25%, but does not influence the decision on approvability of this product.”

“No clinical signs were observed in any animal study that could suggest nasal cavities and/or throat irritation.”

“There was no designated fertility study conducted, however the results of the 2- generation study suggested that the NOAEL for male fertility was 20 mg/kg/day, which provides a safety margin of X with the MRHD of mg/kg for a 60 kg human.”

“Safety pharmacology and genotoxicity batteries were complete and acceptable as were embryofetal toxicity studies in 2 species, i.e., the rat and the rabbit, and a 2-generation reproductive toxicity study in the rat to cover both male fertility and reproductive and developmental toxicity of the product.”

“Considering the exposure to Lotilaner was relatively constant in the dog study by oral exposure, this reviewer found the design of monthly administration in the dog acceptable for assessing systemic toxicity in the context of a daily ocular exposure in humans for 6 weeks.”