2-Year Data Demonstrated Achievement of Key Motor Milestones in Children with SMA Treated with Evrysdi

Two-year data from the ongoing phase 2 RAINBOWFISH clinical trial (NCT03779334) showed that the majority of children with spinal muscular atrophy (SMA) treated with Evrysdi (risdiplam; Genentech, South San Francisco, CA) presymptomatically as infants achieved key motor milestones. According to the results presented at the 29th Congress of the World Muscle Society (WMS), at 2 years children with SMA were able to swallow and feed orally, did not require ventilation, and had cognitive skills typical of children without SMA.

RAINBOWFISH is a phase 2 open-label, single-arm, multicenter clinical trial evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of treatment with Evrysdi for 23 children who had a genetic diagnosis of presymptomatic SMA at age <6 weeks. All participants received Evrysdi once daily as an oral dose selected to achieve target exposure range. The primary endpoint was the percentage of participants with 2 copies of the survival motor neuron (SMN2) gene and a compound muscle action potential (CMAP) of at least 1.5 mV at baseline who were able to sit without support at 12 months, which was achieved in 81% of participants in the overall population.

After 2 years of treatment:

• All children were able to swallow and feed orally, and none required permanent ventilation.
• Children showed cognitive skills typical of children without SMA per the Bayley Scales of Infant and Toddler Development (BSID-III) Cognitive Scale.
• All children with 2 copies of SMN2 (n=5) could sit (100%), and most could stand and walk independently (60%).

Additionally, all children with ≥3 copies of SMN2 (n=18) treated with Evrysdi achieved standing and walking milestones(100%), assessed by Hammersmith Infant Neurological Examination (HINE-2) and BSID-III.

“These 2-year findings confirm the potential of early intervention with Evrysdi to meaningfully improve the lives of children with SMA,” said Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development at Genentech. “Working in tandem with newborn screening programs, Evrysdi is the only noninvasive SMA treatment that can be administered during a child’s first hours of life.”

The most common adverse events (AEs) were teething, gastroenteritis, diarrhea, eczema, and pyrexia, which were consistent with other trials of Evrysdi treatment for SMA. There were no deaths or AEs leading to treatment withdrawal or discontinuation, and the majority of AEs were not considered treatment related.