New Two-Year Data Shows Early Evrysdi Treatment Significantly Improves Motor Milestones in Infants with Spinal Muscular Atrophy

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Two-year data from the Phase II RAINBOWFISH trial (NCT03779334) demonstrated that early treatment with Evrysdi (risdiplam) in infants with pre-symptomatic spinal muscular atrophy (SMA) produced significant motor milestone achievements, such as oral feeding and swallowing, without requiring permanent ventilation.^1,2 Evrysdi, a survival motor neuron 2 (SMN2) splicing modifier, was approved by the FDA in August 2020 to treat SMA in patients aged two months and older. The approval was granted based on data from a clinical trial program that included patients as young as two months of age up to adults aged 60 years with various symptoms and motor function.3 Evrysdi has been found to produce clinically meaningful improvements in motor function in patients from various age groups and with different levels of disease severity, including SMA types 1, 2, and 3.³

“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,” Laurent Servais, MD, PhD, Professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre, said in a press release. “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.”¹

Patients with SMA, a rare genetic disorder, experience the loss of motor neurons in the spinal cord and brainstem, which causes progressive muscle weakness and atrophy. SMA primarily impacts muscles involved in activities such as crawling, walking, swallowing, and breathing. SMA can range from severe cases that develop during infancy to milder forms of the disease that manifest later in life. The disease can be life-threatening, specifically with the more severe forms, such as SMA type 1.

The open-label, single-arm, multicenter RAINBOWFISH trial evaluated Evrysdi for efficacy, safety, pharmacokinetics, and pharmacodynamics in 26 patients aged from birth to six weeks of age at administration of first dose who have genetically diagnosed SMA but have yet to show symptoms. All patients in the trial who were administered Evrysdi (n=18) and who have three or more copies of SMN2 achieved standing and walking milestones as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and Hammersmith Infant Neurological Examination, Module 2 (HINE-2). Most of these patients achieved standing and walking milestones within the windows of typical child development set by the World Health Organization.

Among patients in the trial with two SMN2 copies (n=5), all could sit and 60% were able to stand and walk independently after two years of treatment with Evrysdi. Following two years of treatment, all children could swallow and consume food orally without needing permanent ventilation. Prior research has shown that without disease-modifying treatment, patients with type 1 SMA would not achieve these milestones and typically do not live past two years of age.

In terms of neurological development, the investigators found that after two years of treatment with Evrysdi, children demonstrated cognitive skills that are typical of children without SMA, as per the BSID-III Cognitive Scale.

The safety profile of Evrysdi was consistent with adverse events (AEs) reported in other trials of the drug in patients with SMA. There were no deaths or AEs that caused withdrawal or discontinuation.

The most common AEs reported in the trial were teething, gastroenteritis, diarrhea, eczema, and pyrexia. Investigators noted that these AEs were more indicative of normal aging than underlying SMA, as they were not considered to be related to treatment and resolved over time.

“These two-year findings confirm the potential of early intervention with Evrysdi to meaningfully improve the lives of children with SMA,” Levi Garraway, MD, PhD, Genentech/Roche chief medical officer and head of Global Product Development, said in a press release. “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.”¹

References

1. Majority of Children With Spinal Muscular Atrophy (SMA) Treated With Genentech’s Evrysdi Are Able to Sit, Stand and Walk Independently, Two-Year Data Demonstrate. News release. Genentech. October 13, 2024. Accessed October 14, 2024. https://www.gene.com/media/press-releases/15040/2024-10-13/majority-of-children-with-spinal-muscula

2. A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (Rainbowfish). ClinicalTrials.gov. Updated September 19, 2024. Accessed October 14, 2024. https://clinicaltrials.gov/study/NCT03779334

3. FDA Approves Genentech’s Evrysdi (risdiplam) for Treatment of Spinal Muscular Atrophy (SMA) in Adults and Children 2 Months and Older. News release. Genentech. August 7, 2020: Accessed October 14, 2024. https://www.gene.com/media/press-releases/14866/2020-08-07/fda-approves-genentechs-evrysdi-risdipla