To investigate the efficacy, safety and pharmacokinetics/pharmacodynamics of risdiplam in infants with genetically diagnosed presymptomatic spinal muscular atrophy (SMA).

RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter study that is actively enrolling infants from birth–6 weeks of age (at first dose), regardless of SMN2 copy number. The primary analysis will be conducted at 12 months in infants with two SMN2 copies and compound muscle action potential (CMAP) amplitude ≥1.5mV at baseline.

The primary endpoint is the proportion of infants sitting without support for ≥5 seconds (assessed by Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, Third Edition). Secondary endpoints include the development of clinically manifested SMA; survival and permanent ventilation; achievement of motor milestones; motor function; growth measures; nutritional status; CMAP; pharmacokinetics; and safety monitoring.

As of the data cut-off (20 February 2021), the median age at first dose was 28.5 days (range: 16–40 days) for the first 12 enrolled infants. No treatment-related serious adverse events were reported in infants treated for up to 18.1 months. Efficacy data from infants receiving risdiplam for ≥12 months (n=5) demonstrated that these infants reached a Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders score of ≥60 and maintained swallowing and feeding abilities. We will report updated baseline demographics and safety data in enrolled infants, and efficacy data in infants who have received risdiplam for ≥12 months.