Abstract Details

In patients with SMA, motor neuron degeneration begins before symptom onset, due to a deficiency of survival of motor neuron (SMN) protein. Risdiplam is an oral SMN2 pre-mRNA splicing modifier that increases and sustains functional SMN protein levels.

To assess the efficacy and safety of risdiplam (EVRYSDI®) in infants with presymptomatic spinal muscular atrophy (SMA).

RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter study of risdiplam in infants with genetically diagnosed, presymptomatic SMA. The primary endpoint was the proportion of infants with two SMN2 copies and baseline ulnar CMAP amplitude ≥1.5 mV, who were able to sit without support for ≥5 seconds at Month 12 (Item 22, Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition). Secondary endpoints include motor milestone achievement; motor function; nutritional status; growth measures; survival and permanent ventilation; CMAP; development of clinically manifested SMA; and safety monitoring.

The median age at first risdiplam dose was 25.0 (range 16−41) days (n=26). The primary endpoint at Month 12 was met, with 80% of infants (n=5) able to sit without support for ≥5 seconds. Additionally, 7/8 infants with two SMN2 copies were able to sit without support for ≥30 seconds, including all infants with CMAP amplitude <1.5 mV (n=3). At Month 12, all infants were alive without permanent ventilation and no adverse events (AEs) led to withdrawal or treatment discontinuation. Most AEs were not considered treatment-related and resolved over time. One infant met the criteria for development of clinically manifested SMA. At Month 12, 24/26 infants (92%) were able to sit without support, and many were able to stand (21/26 [81%]) and walk (16/26 [62%]), as assessed by the Hammersmith Infant Neurological Examination, Module 2.

RAINBOWFISH is ongoing globally to provide additional data on the efficacy and safety of risdiplam in infants with presymptomatic SMA.