Spinal muscular atrophy: nusinersen likely benefits older children, too

  • Darras BT & al.
  • Neurology
  • 24.04.2019

  • von Susan London
  • Clinical Essentials
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Takeaway

  • Long-term intrathecal nusinersen (Spinraza) therapy appears to be efficacious in children with later-onset spinal muscular atrophy (SMA) up to age 15 years.

 Why this matters

Key results

  • Treatment outcomes by day 1150 visit:
    • Hammersmith Functional Motor Scale–Expanded score:
      • SMA type II: +10.8 points.
      • SMA type III: +1.8 points.
    • Upper Limb Module score:
      • SMA type II: +4.0 points.
      • SMA type III: not reported.
    • 6-Minute Walk Test distance:
      • SMA type II: not reported.
      • SMA type III: +92.0 m.
  • Fairly stable mean compound muscle action potential values.
  • No discontinuations due to adverse events.

Expert comment

  • In an editorial, Emma Ciafaloni, MD, and Barry S. Russman, MD, write, “Should we leverage the principle of extrapolation to support clinical use of nusinersen in older patients with SMA type 3? … If so, uncertainty should be mitigated by using measures of motor function appropriate to the patient’s stage of disease, regular reviews of safety and risks—given the quarterly intrathecal delivery mode—and by incorporating patient-centered reported outcomes.”

Study design

  • 28 children with SMA aged 2-15 years:
    • 11 with type II SMA.
    • 17 with type III SMA.
  • Treatment:
    • Started 253-day, open-label, phase 1b/2a trial, ascending doses (3-12 mg).
    • Interim period of 196-413 days.
    • Continued on 715-day extension study at 12 mg.
  • Main outcomes: measures of motor function, disease activity.
  • Funding: Biogen; Ionis Pharmaceuticals, Inc.

Limitations

  • Open-label design.
  • Small sample.
  • Differing initial doses.
  • Lack of patient-reported outcomes.