N Engl J Med
Presymptomatic treatment promotes motor development in infants with spinal muscular atrophy
Presymptomatic risdiplam initiation in spinal muscular atrophy (SMA) dramatically altered disease trajectory, enabling motor development and survival outcomes not seen in untreated natural history cohorts. These findings support early genetic screening and treatment initiation, potentially redefining standards of care for SMA.
Study details: The RAINBOWFISH open-label, multicenter phase 2 study (NCT03779334) enrolled 26 infants up to ≤6 weeks old with genetically confirmed SMA but no clinical symptoms. Participants received daily oral risdiplam (0.2 mg/kg). Primary endpoint: independent sitting at 12 months in infants with two SMN2 copies and baseline ulnar compound muscle action potential (CMAP) ≥1.5 mV. Secondary endpoints: survival, need for ventilatory or feeding support, and additional motor milestones >24 months.
Results: At 12 months, 81% of infants could sit independently, 54% could stand alone, and 42% could walk alone. Among the five infants with two SMN2 copies and baseline CMAP ≥1.5 mV, 4 of 5 (80%), four achieved independent sitting (95% confidence interval [CI], 28-100). At 24 months, all infants who completed follow-up (n=23) were alive without permanent ventilation or feeding support. Adverse events were infrequent and mostly unrelated to treatment.
Source:
Finkel RS, et al; RAINBOWFISH Study Group. (2025, August 14). N Engl J Med. Risdiplam in Presymptomatic Spinal Muscular Atrophy. https://pubmed.ncbi.nlm.nih.gov/40802943/