Current Series: Advances in the Treatment of Spinal Muscular Atrophy

Crystal Proud, MD: STR1VE was a phase 3 clinical trial that expanded upon the data that were gathered from the START study. It was multicenter, open label, treating patients with symptomatic SMA [spinal muscular atrophy] type I at less than 6 months of age. As of the 31st of May 2019, the study was fully enrolled, with 17 of 19 patients surviving. That's 89% who reached 13.6 months at the data cut off. This was compared to the 25% survival in the untreated natural history. 
 
The mean CHOP INTEND [Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders score] was 32; 50% of patients sat independently for greater than or equal to 30 seconds at a mean of 8.2 months post treatment, and 83% of patients over 18 months old sat independently for greater than 30 seconds. If we think back to the term type I infant, we know that these are children who were expected to never reach the ability to sit. Nancy, this trial was supportive to enable FDA approval of gene transfer. How did this impact your practice? 
 
Nancy L. Kuntz, MD: Well, it provides an alternative or an option for treatment for children under the age of 2 with spinal muscular atrophy and is something that all of the families that I've met who are aware, either because of family history or now the new, newborn screening, are very interested in addressing. One of the appeals here is that it is a single treatment. Then the children have been followed, and the very young children have appeared to do very well. 
 
As John mentioned, there are adverse effects, but these appear to be transient and without permanent sequela, for the most part. There is a trial that I believe is still ongoing but with some preliminary data on treating pre-symptomatic children. But even waiting for the children to develop the symptoms, as in this case, they had as you'd mentioned, very improved outcomes compared to the untreated natural history, where children without artificial supportive ventilation or nutrition and without any pharmacological treatment do not survive with spinal muscular atrophy. 
 
It is amazing if you've been around for a number of decades watching infants with spinal muscular atrophy to see individuals begin to sit independently and make those motor milestones. The rule of thumb that we should share with the new generation of primary care pediatricians and neurologists is that it used to be that, from the time of diagnosis, there was no progress with motor skills, no new milestones achieved. With this kind of treatment, the children are doing amazingly well.  
 
Crystal Proud, MD: Thank you for sharing that with us. You made mention of evaluation of this particular treatment in pre-symptomatic infants.