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

RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter, global clinical study enrolling infants aged from birth–6 weeks of age (at first dose), regardless of SMN2 copy number. Infants will receive risdiplam for 24 months, followed by a 36-month extension. Primary analysis will be conducted at 12 months of treatment 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 at least 5 seconds after 12 months of treatment (assessed by 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, PK, safety monitoring, and other clinical parameters.

The median age at first dose (range) for the first seven enrolled infants was 35 (16–40) days. We will report updated baseline demographics and baseline SMN protein data in enrolled infants with presymptomatic SMA. Additional preliminary data will also be presented.

RAINBOWFISH will provide valuable information about the effects of risdiplam treatment at the presymptomatic stage in young infants with SMA. Recruitment for the study is ongoing worldwide.