Majority of children with spinal muscular atrophy (SMA) treated with Evrysdi (risdiplam) are able to sit, stand and walk independently, two-year data demonstrate

The study found the majority of children achieved key motor milestones, were able to swallow and feed orally, and demonstrated cognitive skills typical of children without SMA, with none requiring permanent ventilation.

“In children with SMA, motor neuron degeneration starts before the onset of symptoms, so time is of the essence if we hope to preserve muscle function,” said Laurent Servais, M.D., Ph.D., Professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre. “It’s heartening to see that through early intervention with Evrysdi these children have achieved important milestones like sitting, standing and walking that would typically be unattainable without treatment.”

All of the children treated with Evrysdi who had three or more SMN2 copies (n=18), achieved standing and walking (100%) milestones as assessed by Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and Hammersmith Infant Neurological Examination, Module 2 (HINE-2), with most achieving these milestones within World Health Organization (WHO) windows of typical child development. Among the children with two SMN2 copies (n=5), all could sit (100%) and most could stand and walk (60%) independently after 2 years of treatment. After 2 years of treatment, all children were able to swallow and feed orally and none required permanent ventilation. Natural history studies indicate that without disease-modifying treatment, children with Type 1 SMA would not be able to reach such milestones, nor typically live past the age of 2. 

 After 2 years of Evrysdi treatment, children in the study showed cognitive skills typical of children without SMA, as assessed by the BSID-III Cognitive Scale. This study was the first clinical trial in SMA to assess cognition as an exploratory endpoint using a standardized scale. 

“These 2-year findings confirm the potential of early intervention with Evrysdi to meaningfully improve the lives of children with SMA,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Working in tandem with newborn screening programs, Evrysdi is the only non-invasive SMA treatment that can be administered during a child’s first hours of life.” 

To assess outcomes of early treatment initiation before the onset of symptoms, children in the study started treatment with Evrysdi before 6 weeks of age (median age of first dose was 25 days). The study analyzed outcomes against the number of copies of the SMN2 gene each child had. Generally, fewer SMN2 copy numbers are associated with more severe SMA. 

There were no deaths or adverse events (AEs) leading to withdrawal or treatment discontinuation. The most common AEs were teething, gastroenteritis, diarrhea, eczema and pyrexia. The AEs observed in the year-2 analysis are generally consistent with those AEs seen in other Evrysdi trials in SMA. AEs were more reflective of age than underlying SMA. The majority of AEs were not considered treatment-related and resolved over time. 

Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.