Risdiplam treatment in children, teenagers, and adults with later-onset spinal muscular atrophy (SMA) and varying disease duration showed significant improvement in motor function, according to a study published in the Journal of Neurology. Over 24 months, Risdiplam resulted in further improvement/stabilization in the motor function, with an improved safety profile confirming the benefit of longer-term treatment.

Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is caused by the reduced levels of survival of motor neuron (SMN) protein due to homozygous deletions or loss-of-function mutations in the SMN1 gene.

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Patients with type 2 SMA typically exhibit symptoms between 6 and 18 months of age. They get the ability to sit on their own and may occasionally stand or take a few steps with support but are unable to walk independently. In contrast, type 3 SMA patients develop symptom onset after 18 months of age and can walk independently, although this may be temporary. The type 2 and 3 SMA patient population encompasses individuals of different age groups ranging from children to adults with varying functional abilities, contractures, and scoliosis.

This multicenter study included a total of 180 patients who were nonambulant and 2 to 25 years of age, with a genetically confirmed diagnosis of 5q-autosomal recessive SMA, and exhibited clinical symptoms attributable to those of type 2 or type 3 SMA.

Patients were randomized 2:1 with concealed allocation to receive either risdiplam or placebo daily for 12 months. For patients weighing < 20 kg, the risdiplam dose was 0.25 mg/kg, while those weighing ≥ 20 kg were given a 5 mg dose. After 12 months, patients receiving a placebo were switched to risdiplam in a blinded manner, and all patients were treated with risdiplam until month 24. All patients who received at least one dose of risdiplam (n=120) or placebo (n=60) were included in the safety evaluable population.

Efficacy endpoints were summarized through the randomized treatment (risdiplam or placebo switched to risdiplam) for the all-exposure-to-risdiplam treatment period, while for the external comparator analysis, Motor Function Measure (MFM) total score was used for all analyses to compare motor function at month 24.

Study results revealed that patients who initially received risdiplam treatment had the mean change from baseline in MFM32 total score at month 24 to be 1.8 (95% CI 0.7 to 2.9), while 58% of patients exhibited stabilization in their MFM32 total score and 32% achieved an improvement of ≥ 3 in MFM32 total score after 24 months of risdiplam treatment. On the other hand, patients who initially received placebo treatment have the mean change from adjusted baseline in MFM32 total score to be 0.3 (95% CI 0.7 to 1.3) after 12 months of risdiplam treatment.

“The SUNFISH Part 2 24-month data demonstrate the clinically meaningful benefits of risdiplam and reinforce a positive benefit–risk profile for the treatment of children, teenagers, and adults with later-onset SMA,” the authors concluded.


Oskoui M, Day JW, Deconinck N. et al. Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA). J Neurol. Published online February 3, 2023. soi: 10.1007/s00415-023-11560-1