Submitted by David R. Mayans, MD, News Science Editorial Board
Additional comments by David B. Rosenfield, MD, News Science Editorial Board
Mercuri E, et al. Nusinersen versus sham control in later-onset spinal muscular atrophy
. N Engl J Med
Over the last year, we have highlighted a couple of articles involving Nusinersen as a novel treatment for spinal muscular atrophy (SMA). Another trial has been completed and the data was shared in this article. The initial trial data involved children with SMA type 1 diagnosed within the first 2-6 months. This trial involved patients diagnosed with SMA with symptom onset after 6 months of age and their age at the onset of the trial between 2 and 12. There were a few exclusion criteria including the need for invasive or non-invasive ventilation, contractures, severe scoliosis, or gastric tube.
Patients were divided into 2 treatment groups, less than 6 years of age and older than 6 years of age. They were randomly assigned in a 2:1 fashion to treatment with Nusinersen versus sham procedure. Nusinersen was administered on days 1, 29, 85, and 274. Eighty-four were assigned to the Nusinersen group and 42 were in the control group. The patients were followed for 15 months. The primary endpoint of the study was a change in the Hammersmith Functional Motor Scale-Expanded (HFMSE). An interim analysis showed a significant improvement in the treatment group compared to placebo so the trial was terminated early. More than half of the treatment group had a clinically significant improvement in the HFMSE score while only 26% of the placebo group had improvements.
Dr. Mayans’ Comments:
This is another study adding to the growing body of evidence that Nusinersen is effective at not only slowing the progression of SMA, but leading to improvements in strength and gain of function in SMA patients. Previous studies looked at the SMA type 1 population showing effectiveness and safety of treatment starting under 6 months of age. This trial had older patients (average age of 3 years) and shows the effectiveness of this medication in an older SMA population. While this may seem like “old news” due to the studies on younger kids over the last year, this study and treatment are truly groundbreaking in the treatment of this disease.
Dr. Rosenfield’s Summary and Comments:
In 2016, Nusinersen (marketed as Spinraza) became the first medication FDA approved for treating SMA. The medicine is intrathecally administered to treat SMA with a mutation in SMN1. SMA is caused by loss of function mutation in the SMN1 gene which codes for survival motor neuron (SMN) protein. Patients survive due to low amounts of the SMN protein produced from the SMN2 gene. Nusinersen modulates alternate splicing of the SMN2 gene, functionally converting it into an SMN1 gene, thus increasing the level of SMN protein in the CNS.