Pediatric Investigation Plans for seizure and epilepsy treatments: An analysis since the implementation of the European Pediatric Regulation in 2006

Abstract Objective A Pediatric Investigation Plan (PIP) implemented under the European Pediatric Regulation (EC No. 1901/2006) aims to ensure early and systematic evaluation of medicines for children. We analyze PIPs for antiseizure medications (ASMs) submitted to the European Medicines Agency (EMA) since 2006, characterizing their content, focusing on pediatric drug development plans, and describing regulatory outcomes. Methods We reviewed the EMA public database to identify all PIPs (January 2006–July 2025) related to ASMs. Data extracted included target indications, age ranges, trial designs, and approval status. We cross‐checked trials listed in PIPs with EU and US clinical trial registries. Results We identified 22 PIPs for 18 compounds: 13 addressing pediatric epilepsies (11 ASMs) and nine focused on rare epilepsy syndromes (seven ASMs). Focal seizures were the most frequent indication, followed by basket trials including multiple seizure types and syndromes. Rare epilepsy PIPs focused on Dravet syndrome, Lennox–Gastaut syndrome, and tuberous sclerosis complex. Six PIPs achieved full EMA compliance, with an average completion time of 5.6 years. Discrepancies were noted between planned and registered trials. Significance Over nearly 2 decades, PIPs have expanded pediatric epilepsy research beyond focal seizures and have supported orphan drug development. However, limited diversification in targeted syndromes, incomplete trial execution, and limited compliance rates represent persistent challenges for pediatric ASM development.