Concentration-QTc analysis has become a common approach for evaluating proarrhythmic risk and delayed cardiac repolarization of oncology drug candidates. Significant heart rate change has been associated with certain classes of oncology drugs and can result in over- or under-estimation of the true QT prolongation risk.
Jurgen Langenhorst together with collaborators at Genentech, leveraged data from the clinical development program of giredestrant to evaluate the suitability of a novel spline-correction method, while simultaneously evaluating the QT-prolongation risk of the study drug.
They concluded: “The spline-correction method demonstrated superior functionality to reduce the correlation between QTc and heart rate as compared with the traditionally used Fridericia correction. Using either Fridricia or the spline-correction demonstrated that giredestrant has a low risk of prolonging the QT interval at clinically relevant concentrations.”
Pharmetheus affiliate: Jurgen Langenhorst