Risdiplam: A Small Molecule mRNA Splice Modifier Approved to Treat SMA Disease

Risdiplam is the only approved small molecule mRNA splice modifier to date. Over more than five years since its first approval, thousands of patients with spinal muscular atrophy have benefited from risdiplam therapy. Yet, the nonclinical development of risdiplam was marked by toxicological challenges requiring new strategies and approaches, which ultimately translated into clinical success. This minireview covers key aspects of the nonclinical development of risdiplam, particularly focusing on its toxicological characterization and histopathological features in animal studies.