Current Series: Advances in the Treatment of Spinal Muscular Atrophy

Crystal Proud, MD: Julie, I was hoping you could review for us the concept of the SPR1NT trial and implications that it might have regarding early treatment for patients with SMA [spinal muscular atrophy]. 
Julie Parsons, MD: Sure. The SPR1NT trial was done for babies under 6 weeks of age who clearly needed to be pre-symptomatic to be enrolled. One thing that's interesting about the SPR1NT trial is that it was pivotal and very important in terms of pushing forward the concept of newborn screening for SMA and early treatment. The patients were divided into 2 groups: one with 2 copies of SMN2 gene, one with 3 copies of SMN2.  
They were about equally divided, 14 in the 2 copy number group and then 15 in the 3 copy number group. Interestingly, as these kids have been followed—and the study was fully enrolled and the cutoff data that we have are from the end of 2019—we know that, in terms of gross motor achievement, 50% of the children who had 2 copies of SMN2 who were treated pre-symptomatically had normal gross motor milestones, and 100% had normal fine motor milestones. In the babies who had 3 copy numbers, 100% had normal gross motor milestones, and about 93% had normal fine motor milestones.  
All of the babies were continuing to grow and achieve and did not need to have artificial ventilation of any type. The majority had nearly normal feeding without gastrostomy tubes and supplemental feeding. In this group of patients who were treated under 6 weeks of age with single-time therapy, the outcomes were absolutely amazing.  
It still is important, as John was going through the delineation of copy numbers of SMN2, to be able to look at prognosis. We still see that there's a difference between the populations of patients who have 2 copy numbers of SMN2 versus 3 copy numbers of SMN2, so it's important to always keep that in mind. Overall, the achievement of these babies who are treated early on, pre-symptomatically, is absolutely incredible. 
Crystal Proud, MD: Absolutely. Now there was an integrated safety report that was released at the recent 2020 MDA [Muscular Dystrophy Association Clinical and Scientific Conference]. It stated that, as of March 8, 2019, 75 patients have received onasemnogene [abeparvovec-xioi] across 4 clinical trials. New deaths were reported deemed not relevant to treatment. Fever was reported in 40%; 11% experienced liver transaminase elevation, which resolved with prednisolone, and were clinically asymptomatic. There was transient thrombocytopenia noted without clinically significant bleeding or bruising. 
We've all mentioned the importance of discussing potential for adverse effects and the role that the neurologist plays in helping to guide this discussion with the family, reviewing risks and benefits and managing any potential adverse effects that may occur, as well as continuing that interdisciplinary care that we have reviewed that is absolutely critical to the ongoing health of our patients with SMA.  
Despite any treatment, we know that that continued care and continued guidance within the clinic is going to be critical to optimize the health of our patients impacted by spinal muscular atrophy. I’m incredibly hopeful for this patient population and their families, and I think that the future is bright with regard to more of the opportunities for treatment that we have.