Guinea pig dermal sensitisation study (modified Buehler) negative: no erythema after topical application
“A sensitization Study of CK-3773274 by Dermal Administration in Guinea Pigs – Modified Buehler Design Negative, aficamten did not induce erythema after 48 hours of topical application.”
Reversible melanin binding: higher levels in pigmented skin, prolonged retention in eye uveal tract
“Pigmented skin showed higher concentrations of radioactivity than nonpigmented skin, which, together with the prolonged presence of radioactivity in eye uveal tract, indicated (reversible) melanin binding.”
Exaggerated pharmacology: cardiac toxicity (dilated cardiomyopathy, heart failure) in healthy animals near clinical exposure
“Cardiac effects were, unsurprisingly, observed in repeat-dose toxicology studies conducted in rats and dogs at or near exposure levels anticipated for clinical use, which were interpreted as direct results of the intended pharmacology in healthy animals.”