Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA)

Expert Opin Investig Drugs. 2022 May;31(5):451-461. doi: 10.1080/13543784.2022.2056836. Epub 2022 Apr 11.


Introduction: Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disease which is characterised by muscle atrophy and early death in most patients. Risdiplam is the third overall and first oral drug approved for SMA with disease-modifying potential. Risdiplam acts as a survival motor neuron 2 (SMN2) pre-mRNA splicing modifier with satisfactory safety and efficacy profile. This review aims to critically appraise the place of risdiplam in the map of SMA therapeutics.

Areas covered: This review gives an overview of the current market for SMA and presents the mechanism of action and the pharmacological properties of risdiplam. It also outlines the development of risdiplam from early preclinical stages through to the most recently published results from phase 2/3 clinical trials. Risdiplam has proved its efficacy in pivotal trials for SMA Types 1, 2, and 3 with a satisfactory safety profile.

Expert opinion: In the absence of comparative data with the other two approved drugs, the role of risdiplam in the treatment algorithm of affected individuals is examined in three different patient populations based on the age and diagnosis method (newborn screening or clinical, symptom-driven diagnosis). Long-term data and real-world data will play a fundamental role in its future.

Keywords: Central nervous system (CNS); RNA splicing modifier; SMN protein; SMN1 gene; SMN2 gene; neuromuscular disorders; risdiplam; spinal muscular atrophy (SMA).

Publication types

  • Review

MeSH terms

  • Azo Compounds / adverse effects
  • Humans
  • Infant, Newborn
  • Motor Neurons
  • Muscular Atrophy, Spinal* / drug therapy
  • Muscular Atrophy, Spinal* / genetics
  • Pyrimidines
  • RNA Splicing
  • Rare Diseases / drug therapy
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 2 Protein / genetics


  • Azo Compounds
  • Pyrimidines
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein
  • Risdiplam