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Infants with spinal muscular atrophy (SMA) administered early treatment with Evrysdi (risdiplam) demonstrated motor milestone achievements that would not have been reached without pharmaceutical intervention, according to new data from the Phase II RAINBOWFISH trial (NCT03779334) published by The New England Journal of Medicine (NEJM).^1,2

Evrysdi Phase II RAINBOWFISH Trial Shows Early Motor Gains in Presymptomatic SMA Infants

These findings highlight the potential of Evrysdi to change the trajectory of SMA when the treatment is administered shortly after birth, offering an oral therapy option that can be initiated at home, the trial investigators noted.

“This study showed that infants in whom type 1 SMA was predicted to develop who were treated presymptomatically with risdiplam within the first 6 weeks after birth survived without assisted ventilation and achieved motor milestones over a period of 24 months,” the authors wrote in NEJM. “These functional outcomes have not been attainable with supportive care alone.”¹

SMA disease characteristics

• SMA is a rare genetic disorder in which patients lose motor neurons in the spinal cord and brainstem, leading to progressive muscle weakness and atrophy.
• SMA primarily affects 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.

Early treatment with Evrysdi improves motor milestones in SMA

• Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier granted FDA approval in August 2020 to treat SMA in patients aged two months and older.
• The approval was based on data from a clinical trial program that included patients as young as two months of age up to adults 60 years of age 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

Study design of the Phase II RAINBOWFISH trial

• 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 at administration of first dose with genetically diagnosed SMA but who have yet to show symptoms.
• Data from the trial released in October 2024 show that 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.

Two-year efficacy outcomes highlight functional independence

• The preliminary dala also show that after two years of treatment with Evrysdi, all patients in the trial with two SMN2 copies (n=5) were able to sit and 60% were able to stand and walk independently.
• All children were able to swallow and consume food orally without needing permanent ventilation.⁴
• The new data found that following 12 months of treatment with Evrysdi, 81% of infants were able to sit unsupported for 30 seconds, 54% could stand alone, and 42% could walk alone.
• Four of five infants (80%; 95% confidence interval, 28 to 100) with two SMN2 copies and a baseline ulnar CMAP amplitude of at least 1.5 mV could sit without support for at least 5 seconds.
• Among 23 infants who completed two years of treatment, all were alive without needing permanent ventilation or feeding support.

Safety profile of Evrysdi in presymptomatic infants

• In terms of safety, over two years there were nine treatment-related adverse events observed in seven infants but none were deemed serious.
• Three infants were withdrawn by a parent or caregiver following a 12-month visit.

Comparison with NURTURE and SPR1NT trials

“The apparent effects of risdiplam were evident across the spectrum of patients treated, but infants with higher SMN2 copy numbers and CMAP amplitudes appeared to have more favorable responses,” the study authors concluded. “Target drug-exposure levels were achieved, and the majority of adverse events were not considered to be treatment related and resolved over time.

“Risdiplam may be a therapeutic option for treatment of presymptomatic SMA, with the advantage of rapid initiation of oral administration at home. Larger comparative trials with longer follow-up are warranted to further understand its relative safety and efficacy.”¹

References

1. Finkel R., et al. Risdiplam in Presymptomatic Spinal Muscular Atrophy. N Engl J Med 2025;393:671-682. DOI: 10.1056/NEJMoa2410120. VOL. 393 NO. 7.

2. A Study of Risdiplam in Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy (Rainbowfish). ClinicalTrials.gov. Updated August 24, 2025. Accessed August 27, 2025. 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 August 27, 2025. https://www.gene.com/media/press-releases/14866/2020-08-07/fda-approves-genentechs-evrysdi-risdipla

4. 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 August 27, 2025. https://www.gene.com/media/press-releases/15040/2024-10-13/majority-of-children-with-spinal-muscula