Real-world Data Find Nusinersen Safe and Effective in Patients With SMA1

A retrospective observational cohort study of patients ranging in age from infants to adults provides real-world evidence that nusinersen is safe and effective for those with SMA1.

Patients with spinal muscular atrophy (SMA) treated with nusinersen have seen promising results in clinical trials, and a real-world multinational study found further evidence the treatment is safe and beneficial in SMA type 1 patients ranging from infants to adults.

SMA is caused by deletion or mutations of the survival motor neuron 1 (SMN1) gene, and phenotypes are based largely on motor function and age of onset. Type 1 SMA (SMA1) is the most common, and infants affected by this phenotype typically never achieve independent sitting. Babies with SMA1 typically have a life expectancy of less than 2 years.

Nusinersen is an antisense oligonucleotide that enables the SMA2 gene — which typically does not produce adequate SMN protein to compensate for loss or mutation of SMA1 — to produce greater numbers of full-length SMN proteins and partially compensate for SMA1 mutation or deletion. Clinical trials have shown promising survival and motor milestone outcomes in patients with SMA1 treated with nusinersen.

The retrospective observational cohort study, published in the Journal of Neurology, Neurosurgery, and Psychiatry, included data on baseline clinical characteristics, motor outcomes, and ventilation needs of SMA1 patients treated with nusinersen at 8 institutes in Hong Kong, Taiwan, and South Korea. Patients started nusinersen as part of the Expanded Access Program (EAP) between 2017 and 2019.

Baseline information included newborn screening when applicable, gestational age at birth, age of symptom onset, SMN1 mutation, SMN2 copy number, sex, weight, respiratory support status, feeding status, musculoskeletal status, and age at treatment initiation.

The Hammersmith Infant Neurologic Examination Part 2 (HINE-2) motor milestones score, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), and motor milestone achievements were used to gauge motor outcomes. Patients were assessed pretreatment (M0), at 6 months post-treatment (M6), and at 10 months post-treatment (M10). Meaningful improvement was defined as a 4-point or greater increase of CHOP INTEND and a 5-point or more increase of HINE-2 score.

A total of 40 patients with SMA1 were included in the study cohort, and all began treatment after symptom onset. Overall, 57% began treatment at 2 years old or younger, with a median initiation age of 20 months. Nine patients were identified by newborn screening, and 8 of those patients began treatment at less than 7 months old.

Patients who began treatment at 2 years old or younger showed more advanced motor milestones. Of those patients, 36.4% were able to sit up without assistance and 13.6% were able to stand with assistance. In contrast, 6.7% of patients who began treatment after 2 years of age were able to sit without assistance.

At M10, 61.1% of patients who started treatment before age 2 gained at least 5 points on the HINE-2 assessment, versus 7.1% of patients who started after 2 years old. Patients with 3 SMN2 copies had better motor response than those with only 2 copies of the gene.

Newborn screening, time between symptom onset and treatment initiation (disease duration), and baseline HINE-2 scores were predictive of outcomes. Delta HINE-2 (M10-M0) scores were negatively correlated with disease duration, positively correlated with baseline HINE-2 scores, and positively correlated with newborn screening.

Overall, these real-world findings provide evidence that nusinersen is safe and benefits patients with SMA1 ranging from infants to adults. Additionally, the findings align with others suggesting that newborn screening holds potential to maximize treatment efficacy by promoting early treatment initiation in infants.


Chan SH, Chae J, Chien Y, et al. Nusinersen in spinal muscular atrophy type 1 from neonates to young adult: 1-year data from three Asia-Pacific regions. J Neurol Neurosurg Psychiatry. Published online February 11, 2021. doi:10.1136/jnnp-2020-324532