Risdiplam (EVRYSDI) is approved for the treatment of patients with spinal muscular atrophy ≥ 2 months old. CYP3A-mediated DDI risk in pediatric patients was evaluated by physiologically-based pharmacokinetic (PBPK) modelling and informed the label.
This talk will illustrate a modeling strategy for the extrapolation of DDIs from adults to children covering:
- Development of a patient-specific growth model
- Validation of the adult PBPK model with independent data
- Estimation of drug specific DDI parameters from clinical data in healthy adults
- Sensitivity assessments of different ontogeny functions for DDI extrapolations from adults to children
- Approach to qualify DDI prediction in children