Vyndaqel: animal efficacy model or human cells?

“The pharmacologic activity of tafamidis was demonstrated only in vitro, through its binding to TTR at the thyroxine binding sites and stabilisation of the TTR tetramer under non-physiologic (acid and urea denaturation conditions) and physiologic conditions.”

“The CHMP considered that at the time of the preclinical development of tafamidis, an animal model of ATTR-PN that would reflect the clinical disease or resemble the pathology was not available, and that none of the transgenic animals described in the literature reproduce the pathology seen in ATTR patients.”

“Since there is no relevant preclinical disease model, the CHMP considered that the best dose regimen was established from understanding of in vitro and ex vivo PK/PD experiments, combined with an extrapolation of clinically observed pharmacokinetics to select a dose that would achieve therapeutically relevant concentrations.”