Risdiplam (Evrysdi®): A Comprehensive Monograph on the First Oral SMN2 Splicing Modifier for Spinal Muscular Atrophy

Executive Summary

Risdiplam, marketed under the brand name Evrysdi®, represents a paradigm shift in the management of spinal muscular atrophy (SMA), a devastating, progressive neuromuscular disorder. As the first small-molecule, orally administered, and systemically distributed disease-modifying therapy for SMA, Risdiplam addresses critical unmet needs left by earlier therapeutic modalities. Its development was a direct response to the significant treatment burdens associated with invasive, facility-based administrations, offering patients a therapy that can be taken at home. The mechanism of action is highly specific: Risdiplam is a Survival of Motor Neuron 2 (SMN2) pre-mRNA splicing modifier that selectively promotes the inclusion of exon 7, thereby correcting the primary molecular defect of the SMN2 gene and enabling the production of full-length, functional Survival of Motor Neuron (SMN) protein. This action is not confined to the central nervous system; as an orally bioavailable small molecule, Risdiplam increases SMN protein levels systemically, addressing the growing understanding of SMA as a multi-system disorder.