Presentation (CTI)

OBJECTIVES: EU Regulation 2021/2282 introduced mandatory Joint Clinical Assessments (JCAs) for new oncology medicines and advanced therapy medicinal products from 2025, while US Food and Drug Administration (FDA) approval remains a regulatory review with different evidentiary objectives. This study developed and pilot-tested a structured framework to compare JCA and FDA evidence expectations for oncology medicines and identify implications for evidence generation.
METHODS: Publicly available documents were reviewed, including the European Commission JCA report and summary materials for tovorafenib and FDA approval and prescribing information documents. Extracted items were mapped across five domains: assessment population/PICO structure, comparator requirements, trial design and evidence-synthesis approach, clinical and patient-reported outcome coverage, and residual evidence gaps affecting relative clinical effectiveness interpretation.
RESULTS: Tovorafenib was the first medicine to complete the EU JCA process. FDA granted accelerated approval for relapsed or refractory BRAF-altered pediatric low-grade glioma based on a multicenter, open-label, single-arm FIREFLY-1 trial, with overall response rate and duration of response as key efficacy measures. The JCA report evaluated evidence within multiple PICO questions and required interpretation against specified comparators and outcomes, including generic and disease-specific health-related quality of life. No randomized direct comparative trial or anchored indirect comparison versus PICO comparators was identified. For one PICO, comparative evidence was based on an unanchored matching-adjusted indirect comparison using FIREFLY-1 and Bouffet 2023 data; for several other PICOs, no comparator evidence or relative-effect evidence was submitted or included. Major uncertainty was attributed to limitations of the indirect evidence base.
CONCLUSIONS: The pilot case demonstrates that evidence supporting FDA accelerated approval may not fully address EU JCA requirements for relative clinical effectiveness. The proposed framework provides a reproducible structure for identifying comparator, design, outcome, subgroup, and evidence-synthesis gaps when oncology products enter both pathways.