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cc-by-nc (c) García Parra, Beliu et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/231547

Real-World Evidence Supporting Orphan Drugs Approvals for Rare Neuromuscular Disorders in the European Union and the United States: Review of Public Assessment Reports (2015–2025)

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Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Assessment Reports and FDA review packages for ODs targeting neuromuscular indications. Each document was screened for mention of RWD sources and by the regulatory weight assigned to the resulting RWE. We identified 14 OD approvals by the EMA and 13 by the FDA, with greater use of RWE by the FDA. Indications comprised spinal muscular atrophy (3/3 EMA/FDA), amyotrophic lateral sclerosis (1/3), amyloid neuropathies (2/2), Friedreich ataxia (1/1), Lambert–Eaton syndrome (1/1), myasthenia gravis (2/2), myotonic disorders (1/0), and Duchenne muscular dystrophy (2/1). Among 18 evaluable dossiers, clinical outcome assessments (COA) were reported as follows: patient-reported outcomes - 39.1%, clinician-reported outcomes - 34.7%, observer-reported outcomes - 13.1 %, and performance outcomes - 13.1%. Only tofersen incorporated all COA types. The use of RWE for the evaluation of ODs is increasing for both the FDA and the EMA, more so for the former than for the latter. Harmonized methodological standards and transparent reporting frameworks are urgently needed to generate quality evidence that benefits stakeholders.

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GARCÍA PARRA, Beliu, et al. Real-World Evidence Supporting Orphan Drugs Approvals for Rare Neuromuscular Disorders in the European Union and the United States: Review of Public Assessment Reports (2015–2025). Current Opinion In Pharmacology. 2025. Vol. 86. ISSN 1471-4892. [consulted: 30 of September of 2026]. Available at: https://hdl.handle.net/2445/231547

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