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

“Aficamten was not mutagenic or clastogenic in a standard battery of genotoxicity studies including the Ames assay and a combined in vivo micronucleus assay and comet assay.”

“There were no aficamten-related tumor findings in a 26-week carcinogenicity study in transgenic rasH2 mice at doses up to 2.0 mg/kg/day or in a 2-year carcinogenicity study in Sprague Dawley rats at doses up to 3 mg/kg/day (corresponding to 4-times the exposure at the MRHD based on AUCunbound).”

“A rat embryofetal development (EFD) study demonstrated an increase in external malformations (kinked tail) at aficamten exposures higher than clinical exposures at the MRHD.”

“Effects observed on electrocardiogram readings after repeated aficamten dosing are typical of cardiac compensation due to the intended pharmacologic action of aficamten. Aficamten and its metabolites did not have inhibitory effects on the hERG channel at clinically relevant concentrations.”