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Risdiplam: A Review in Spinal Muscular Atrophy

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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.

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Acknowledgments

During the peer review process the manufacturer of risdiplam was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Julia Paik

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  1. Julia Paik
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Correspondence to Julia Paik.

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The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest

Julia Paik is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Additional information

The manuscript was reviewed by: B. T. Darras, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA; M. Jędrzejowska, Rare Diseases Research Platform, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland; J. Kirschner, Department of Neuropediatrics, Medical Center – University of Freiburg, Freiburg, Germany.

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Paik, J. Risdiplam: A Review in Spinal Muscular Atrophy. CNS Drugs 36, 401–410 (2022). https://doi.org/10.1007/s40263-022-00910-8

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