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Long-Term Comparative Efficacy and Safety of Risdiplam and Nusinersen in Children with Type 1 Spinal Muscular Atrophy

Christos Kokaliaris1, Rachel Evans2, Neil Hawkins2,3

  • 1F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland. christos.kokaliaris@roche.com.

Advances in Therapy
|May 5, 2024
PubMed

Insights

Risdiplam demonstrated superior long-term efficacy and safety compared to nusinersen for treating spinal muscular atrophy (SMA) type 1 in children. This analysis provides crucial data for healthcare decisions in managing this severe genetic neuromuscular disease.

Area of Science:

  • Neurology
  • Genetics
  • Pediatrics

Background:

  • Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder leading to motor neuron loss and progressive muscle weakness.
  • Type 1 SMA is particularly severe, with affected children unable to sit independently and facing a high mortality rate before age 2 without intervention.
  • Current treatment options lack direct comparative trials, necessitating indirect comparisons for informed healthcare decisions.

Purpose of the Study:

  • To evaluate the long-term efficacy and safety of risdiplam versus nusinersen in pediatric patients with type 1 SMA.
  • To conduct an indirect treatment comparison to mitigate bias from differing baseline characteristics between treatment groups.
  • To provide evidence for healthcare decision-making regarding SMA treatment options.

Main Methods:

  • An unanchored matching-adjusted indirect comparison (MAIC) was performed.
  • Data from 58 children treated with risdiplam in the FIREFISH trial were analyzed.
  • Published aggregate data from 81 children treated with nusinersen in the ENDEAR and SHINE trials (≥36 months follow-up) were utilized.

Main Results:

  • Risdiplam treatment was associated with a 78% reduction in mortality rate and an 81% reduction in the rate of death or permanent ventilation compared to nusinersen.
  • A 57% reduction in serious adverse events was observed with risdiplam versus nusinersen.
  • Children on risdiplam showed a 45% higher rate of achieving a motor milestone response (HINE Module 2) and a 186% higher rate of significant improvement on the CHOP-INTEND scale.

Conclusions:

  • Long-term data suggest risdiplam is a superior treatment option compared to nusinersen for children with type 1 SMA.
  • The findings support risdiplam's efficacy in improving motor function and survival outcomes.
  • This indirect comparison provides valuable insights into the comparative effectiveness of available SMA therapies.
Abstract

Keywords:
Clinical trialIndirect treatment comparisonMAICMatching-adjusted indirect comparisonNeuromuscular diseaseNusinersenPropensity score matchingRisdiplamSMASpinal muscular atrophy

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