MDA 2026: Early Evrysdi treatment linked to milestone gains in SMA infants
RAINBOWFISH results show most children reached and maintained milestones
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- Evrysdi (risdiplam) appears safe in presymptomatic children with SMA.
- Most children reached and maintained motor and developmental milestones over three years.
- No new safety concerns were seen over five years of treatment.
Up to three years of treatment with Evrysdi (risdiplam) appears safe and was associated with presymptomatic children with spinal muscular atrophy (SMA) reaching and maintaining key developmental milestones, according to Phase 2 study results.
“The majority of children treated with [Evrysdi] before the onset of SMA symptoms, maintained motor milestones and bulbar function and showed cognitive skills similar to children without SMA,” the researchers wrote. The long-term data from the Phase 2 clinical trial, RAINBOWFISH (NCT03779334), also supported its safety profile in this population.
Multiple studies presented at MDA highlight Evrysdi outcomes
The research team presented results from RAINBOWFISH and other studies in two posters at the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 8-11 in Orlando, Florida. Several study authors are employees of Roche, which markets Evrysdi with its subsidiary, Genentech.
In SMA, mutations in the SMN1 gene cause a deficiency of the survival motor neuron (SMN) protein, which is essential for the health of motor neurons — the nerve cells that control movement. Low SMN levels cause these cells to degenerate, leading to characteristic symptoms of muscle weakness and wasting.
A backup gene, SMN2, also carries instructions for making SMN protein. However, due to a difference in its genetic code, it produces much less functional protein. Having more copies of SMN2 is generally associated with milder disease.
Evrysdi is a disease-modifying therapy that works by increasing SMN production from the SMN2 gene. In the U.S., it is approved for people of all ages with all types of SMA and is taken orally or through a feeding tube.
The RAINBOWFISH trial evaluated the safety and efficacy of Evrysdi in infants 6 weeks of age or younger who had not yet developed overt symptoms of SMA. The study met its primary goal, demonstrating that 80% of infants with two SMN2 copies in the primary analysis population were able to sit without support for at least five seconds after one year of treatment.
RAINBOWFISH data show milestone gains and long-term outcomes
At the MDA conference, researchers presented long-term trial results in the poster, “RAINBOWFISH: 3-year efficacy and safety data of risdiplam in children with presymptomatic spinal muscular atrophy (SMA).” The analysis included 26 children who began receiving Evrysdi before symptom onset, at a median age of 25 days. A total of 23 completed three years of treatment.
Results showed that most children reached key motor milestones and maintained them over time. Among those who reached three years, 21 of 23 (91%) were able to sit, stand, and walk without support. No children lost abilities once they were achieved during follow-up.
Over three years, all children who completed treatment were able to swallow, indicating preserved bulbar function. One child was fed orally in combination with a feeding tube, with about 10% of feedings delivered this way. Likewise, one child required respiratory support during an illness to assist with coughing.
In addition, cognitive skills and speech development were similar to those of typically developing children without SMA. Scores were similar across groups with different numbers of SMN2 copies. According to the investigators, RAINBOWFISH is the first clinical trial in SMA to report cognitive outcomes in presymptomatic infants.
In a separate poster, “5-year safety update: Risdiplam clinical trial program for spinal muscular atrophy (SMA),” researchers reported safety findings across several Phase 2 studies: RAINBOWFISH, SUNFISH (NCT02908685), FIREFISH (NCT02913482), and JEWELFISH (NCT03032172). While children in RAINBOWFISH were followed for three years, participants in the other three trials were monitored for up to five years.
Combined, the studies included 492 participants, including 466 with symptomatic SMA and 26 presymptomatic children from RAINBOWFISH. Participants spanned a wide range of ages and SMN2 copy numbers. Most symptomatic participants were not able to walk.
Overall, “no new safety patterns were detected in the longer term,” the researchers wrote.
Long-term safety data support Evrysdi use across SMA types
In line with previously reported data, the most common side effects in symptomatic participants included upper respiratory tract infections, vomiting, headache, fever, and the common cold. In presymptomatic children, the most common side effects were upper respiratory tract infections, fever, vomiting, and gastroenteritis (stomach flu).
Among symptomatic participants with SMA types 1–3, the overall rate of side effects and serious side effects decreased over time, with the highest rates seen during the first year of treatment. No treatment-related side effects led to discontinuation of Evrysdi.
The most common serious side effects were infections such as gastroenteritis and pneumonia.
Taken together, Evrysdi “continues to demonstrate a favorable safety profile after 5 years of treatment in a broad range of participants,” the investigators wrote.
Note: The SMA News Today team is providing live coverage of the 2026 MDA Clinical & Scientific Conference March 8-11 in Orlando, Florida. Go here to see the latest stories from the conference.
