Presentation (CTI)

OBJECTIVES: Extending indications to adolescent populations often presents challenges that may limit the generation of robust clinical evidence and increase reliance on pharmacokinetic (PK)-based extrapolation. This study assessed how the Transparency Commission (TC) evaluated adolescent indication extensions in relation to the corresponding adult indications.
METHODS: We systematically reviewed TC evaluations of indication extensions to adolescents issued between 2024 and May 26, 2026, and compared the conclusions with those reached for the corresponding adult indications.
RESULTS: Thirteen adolescent extension indications were identified. Most submissions were supported by phase III, randomized, comparative trials with a primary efficacy endpoint (n=7; 54%), while two were based on phase II/IIb efficacy data. Only four assessments relied solely on PK and safety data, with efficacy extrapolated from adults. Among these, extrapolation was supported either by European anti-infective guidelines based on comparable drug exposure (n=2) or by an EMA Paediatric Investigation Plan (n=1). In the remaining case the TC highlighted the lack of robust pediatric evidence on clinical outcomes and the limited transferability of adult data due to differences in disease presentation; however, these concerns did not result in a less favorable appraisal than that granted in adults. Overall, TC’s conclusions on clinical benefit and clinical added value (CAV) were consistent with those reached in adults for most cases (n=9; 69%). Four evaluations received less favorable ratings (three lower CAV ratings and one lower clinical benefit rating), despite being supported by robust phase III randomized comparative trials.
CONCLUSIONS: Despite the challenges of pediatric drug development, most adolescent indication extensions were supported by robust evidence and received TC evaluations consistent with those of the corresponding adult indications. The limited number of cases relying on extrapolation from adult data did not result in less favorable evaluations, highlighting the TC’s acceptance of extrapolation approaches when supported by an appropriate scientific rationale and regulatory framework.