Newly Published Nusinersen Clinical Data Highlight Positive Data in Children with Spinal Muscular Atrophy

Findings from the Phase 1/2 study evaluating nusinersen in childhood-onset spinal muscular atrophy published in Neurology and the Journal of Child Neurology

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease that is the leading genetic cause of infant mortality. SMA is caused by a loss of, or defect in, the survival motor neuron 1, or SMN1, gene leading to a decrease in SMN protein. SMN is critical to the health and survival of nerve cells in the spinal cord that are responsible for neuro-muscular function. Currently, there are no therapeutic options available to patients with SMA.

Nusinersen is designed to address the genetic cause of SMA by increasing the production of SMN, a protein required to maintain the health and function of motor neurons.   We have reported data from a number of clinical studies in addition to the data published this week in Neurology that suggest nusinersen could provide significant therapeutic benefit to infants and children with SMA.  We and Biogen are currently evaluating nusinersen in two Phase 3 studies that are designed to support applications for marketing approval of nusinersen in infants and children with SMA.

The findings published this week in Neurology were from an open-label, dose-escalation Phase 1/2 study designed to evaluate the safety and tolerability of single doses of nusinersen (1, 3, 6 and 9 mg) administered in children with SMA between two and 14 years of age. In this study, nusinersen was well-tolerated at all dose levels with a safety profile that supported continued development. Encouragingly, in the 9mg dose cohort, a mean improvement of 3.1 points was observed after three months postdose in the Hammersmith Functional Motor Scale Expanded (HFMSE) score, a clinical measure of functional ability. Improvements in muscle function measures were found to be durable in the 9 mg dose cohort with a mean improvement of 5.8 points observed in HFMSE scores nine to 14 months after dosing. A sustained increase of three or more points in HFMSE scores represents a significant departure from the natural course of disease progression with SMA Type 2 and Type 3. Upon completion of dosing in the Phase 1/2 study, the majority of children entered into an open label extension study through which they continue to receive nusinersen and follow up assessments.

In addition, a paper published recently in the Journal of Child Neurology titled, “Intrathecal Injections in Children with Spinal Muscular Atrophy: Nusinersen Clinical Experience” reported that intrathecal administration of nusinersen was safe, well-tolerated and feasible in children with SMA in the above-mentioned Phase 1/2 study. In this study, adverse event frequency was similar to that previously reported in children undergoing this same procedure. Headache, post-lumbar puncture headache and back pain were experienced in a minority of the patients and were considered to be related to the injection procedure and not related to study drug. In addition, the study authors reported that the use of a different needle (smaller gauge or atraumatic) could substantially reduce the procedure-related adverse events.  Taken together, these results support the continued development of nusinersen for the treatment of SMA.


Chiriboga, C. A., K. J. Swoboda, B. T. Darras, S. T. Iannaccone, J. Montes, D. C. De Vivo, D. A. Norris, C. F. Bennett, K. M. Bishop. 2016. Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy. J Neurol. 10.​1212/​WNL.​0000000000002445. Published online before print February 10, 2016.

Hache, M., K. J. Swoboda, N. Sethna, A. Farrow-Gillespie, A. Khandji, S. Xia, and K. M. Bishop. 2016. Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. J Child Neurol. 0883073815627882. First published on January 27, 2016.