The SMART study, a Phase 3b, open-label, single-arm, multicenter study, evaluated the safety, tolerability, and efficacy of Zolgensma in pediatric patients with symptomatic SMA. The study included children weighing between 8.5 kg and 21 kg, with a mean age of 4.69 years. Most participants had previously discontinued another disease-modifying therapy before receiving Zolgensma.
Key findings from the study include:
- Safety and Tolerability: The majority of patients experienced increases in transaminases and transient thrombocytopenia, all of which were asymptomatic and managed with appropriate treatment. No new safety signals were observed.
- Efficacy: Most patients maintained or improved motor milestones from baseline. The mean increase in total Revised Upper Limb Module (RULM) score was 2 points, and the mean increase in total Hammersmith Functional Motor Scale – Expanded (HFMSE) score was 3.7 points. Four patients demonstrated new development milestones at week 52.
- Motor Milestones: Nearly all patients who could sit with slight support maintained this milestone at Week 52. Three patients achieved the milestone of newly standing with support, and one achieved newly walking with support. All patients who could walk at baseline maintained this milestone until the end of the study.
Dr. Hugh McMillan, Pediatric Neurologist, commented on the results, stating, "The results from the SMART study provide evidence that Zolgensma is clinically beneficial for older and heavier patients with SMA, many of whom have had prior treatment with another disease-modifying therapy."
Zolgensma is the only approved gene therapy for SMA, designed to directly address the genetic root cause of the disease by replacing the function of the missing or non-working SMN1 gene. It is now approved in more than 51 countries, with over 3,700 patients treated globally.
The study's findings are significant as they provide evidence supporting the use of Zolgensma in a broader patient population, including older and heavier children with SMA, and those who have previously received other treatments.
