Risdiplam treatment leads to a significant improvement in motor function compared to placebo in patients with spinal muscular atrophy (SMA) type 2 or type 3 and aged 2 to 25 years who are not able to walk, according to results from SUNFISH part 2.

SUNFISH is a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial that aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of risdiplam. The first part of the trial is an exploratory dose-finding part lasting 12 weeks. The second part is a confirmatory study lasting 24 months.

The study already recruited 231 patients, aged 2 to 25 years with a confirmed diagnosis of 5q autosomal recessive type 2 or type 3 SMA who were not able to walk but were able to sit independently, and could at least raise 1 or 2 hands to their mouth.

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Following the part 1 exploratory dose-finding, participants were randomly assigned to receive oral risdiplam at a dose of 5 mg per day if they weighed more than 20 kg, and 0.25 mg per kg per day or a placebo if they weighed less than 20 kg. The primary outcome measure of part 2 of the study was the change from baseline in the total score of the 32-item Motor Function Measure at 12 months, among others.

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The present analysis, which was published in The Lancet Neurology, included data from 115 patients who received risdiplam and 50 patients who received placebos. The results showed that the least-squares mean change at month 12 was 1.36 from baseline in patients receiving risdiplam compared to –0.19 from baseline in those receiving placebos. This corresponds to a difference of 1.55 in favor of risdiplam.

Adverse events were reported in at least 5% more patients receiving risdiplam compared to those receiving placebo and included pyrexia, diarrhea, rashes, mouth and aphthous ulcers, urinary tract infections, and arthralgia. The incidence of serious adverse events was similar between the 2 groups apart from pneumonia which occurred in 8% of those treated with risdiplam compared to 2% of those given placebos.

“Our exploratory subgroup analyses showed that motor function was generally improved in younger individuals and stabilized in older individuals, which requires confirmation in further studies,” the researchers wrote. The trial finished recruiting participants but is still ongoing. The estimated completion date is September 2, 2023.

Risdiplam is an oral disease-modifying treatment that aims to increase the amount of functional survival motor neuron (SMN) protein to be produced from the SMN1 gene, which is mutated in patients with SMA. The treatment is marketed under the brand name Evrysdi® and has already been approved by the US Food and Drug Administration for patients with SMA aged 2 years and above.


Mercuri E, Deconinck N, Mazzone ES, et al. SUNFISH Study Group. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2022;21(1):42-52. doi:10.1016/S1474-4422(21)00367-7