Risdiplam: A Review in Spinal Muscular Atrophy

CNS Drugs. 2022 Apr;36(4):401-410. doi: 10.1007/s40263-022-00910-8. Epub 2022 Mar 13.

Abstract

Risdiplam (Evrysdi®) is the first oral drug developed to treat spinal muscular atrophy (SMA) and is approved in multiple countries worldwide. It is approved for the treatment of SMA in patients aged ≥ 2 months in the USA and the EU, with this approval further specified in the EU for the treatment of 5q-autosomal recessive SMA with a clinical diagnosis of SMA types 1, 2, or 3 or with one to four survival motor neuron 2 (SMN2) copies. As an SMN2 pre-mRNA splicing modifier, risdiplam increases the production of full-length SMN protein, the lack of which drives the pathophysiology of SMA. In phase 2/3 clinical trials, risdiplam significantly improved motor function in infants with SMA type 1 and in patients aged 2-25 years with SMA types 2 or 3. These motor improvements were maintained with up to 2 years of treatment with risdiplam. Risdiplam was generally well tolerated, with a favourable benefit to risk balance. As an oral drug, risdiplam provides a convenient and useful treatment option across a broad range of patient ages and subtypes of SMA.

Plain language summary

Patients with spinal muscular atrophy (SMA) have insufficient levels of survival motor neuron (SMN) protein due to a defect in the SMN1 gene. The SMN2 gene is also able to produce some SMN protein, but not to the amount required to maintain adequate muscle function and form. Risdiplam (Evrysdi®) is a drug that targets SMN2 to improve the production of viable SMN protein and the first oral medication approved for the treatment of SMA. In the FIREFISH and SUNFISH clinical trials, risdiplam improved motor function in patients of all ages, with improvements maintained after 24 months of treatment. Risdiplam was generally well tolerated in these trials, with a favourable benefit to risk balance. As an orally administered treatment, risdiplam provides a convenient and useful treatment option across a broad range of patient ages and subtypes of SMA.

Publication types

  • Review

MeSH terms

  • Azo Compounds / adverse effects
  • Humans
  • Infant
  • Motor Neurons
  • Muscular Atrophy, Spinal* / drug therapy
  • Muscular Atrophy, Spinal* / genetics
  • Pyrimidines* / adverse effects

Substances

  • Azo Compounds
  • Pyrimidines
  • Risdiplam

Associated data

  • figshare/10.6084/m9.figshare.19111877