Avmapki Fakzynja Co-pack: genotox, carcinogenicity and repro: done or skipped?

“Defactinib was not mutagenic in the bacterial reverse mutagenesis (Ames) assay and was not clastogenic in an in vitro Chinese hamster lung cell chromosome aberration assay. Defactinib was positive in the in vitro micronucleus assay through an aneugenic mechanism and in the in vivo rat bone marrow micronucleus assay.”

“The Applicant did not conduct carcinogenicity studies with avutometinib; it is also not warranted to support the marketing application of AVMAPKI FAKZYNJA CO-PACK for the proposed indication.”

“The Applicant did not conduct any reproductive toxicology studies with avutometinib and defactinib.”

“In safety pharmacology studies, avutometinib was found to be a weak inhibitor of the hERG channel current. As such, the data suggests that avutometinib may pose little or no risk for QT interval effects.”