RNA-based medicinal products represent a promising frontier in personalised medicine, offering sequence-specific disease targeting at various molecular levels, yet their clinical translation in the European Union (EU) may be hindered by regulatory uncertainty around definitions and evidence requirements; this study therefore aims to identify commonalities and differences in scientific and clinical characteristics of RNA-based therapeutics assessed by the European Medicines Agency to inform a classification framework supporting regulatory clarity and product development. A qualitative document analysis was conducted on 13 RNA-based therapeutics for non-infectious diseases that applied for EU marketing authorisation by March 2025, using EU regulatory documents including European Public Assessment Reports and Risk Management Plans to analyse descriptive, scientific and clinical characteristics, with data extraction validated via a dual-review process. Of the 13 products, 10 were approved, two refused and one withdrawn; they included five siRNAs, seven antisense oligonucleotides (ASOs) and one aptamer, primarily for rare diseases, with 12 acting through sequence-specific hybridisation to pre-mRNA or mRNA to suppress or modify protein production, often targeting liver diseases using delivery systems like GalNAc conjugation or lipid nanoparticles, while clinical challenges included limited efficacy data (e.g. small trials, surrogate endpoints) and recurring safety concerns including coagulation-related risks for ASOs, and notably risk profiles were not consistently linked to disease targets or RNA sequence. These findings highlight an opportunity for classification based on RNA mechanism and related chemical modifications conveying similar regulatory implications, suggesting that a structured framework could support knowledge pooling, which is especially useful for rare disease indications.
Lewis et al. (Wed,) studied this question.