Intravenous Zolgensma Shows Motor Function Improvement in Heavier Pediatric Patients With SMA


Findings from the recent phase 3b SMART trial affirm the safety and efficacy of intravenous onasemnogene abeparvovec (Zolgensma; Novartis) in spinal muscular atrophy when patient weights range from 8.5 kg to 21 kg.

Sandra P. Reyna, MD, chief scientific advisor and head of global medical engagement for SMA at Novartis

Sandra P. Reyna, MD

Credit: LinkedIn

New findings from the phase 3b SMART trial (NCT04851873) showed that intravenous onasemnogene abeparvovec (Zolgensma; Novartis) demonstrated improvement in motor function among heavier pediatric patients with spinal muscular atrophy (SMA) over 52 weeks, suggesting the clinical benefit of this form of therapy for a heavier weight SMA population who had prior treatment with another disease-modifying therapy.1,2

Among 24 patients with SMA, 7 were in the 8.5- to 13-kg weight group, 8 were in the more than 13- to 17-kg weight group, and 9 were in the more than 17- to 21-kg (n = 9) weight group. Investigators observed that motor function was maintained or showed improvement with the treatment in the majority of patients. At 52 weeks, mean change from baseline was 2.0 (SD, 4.0) for the Revised Upper Limb Module (RULM) score and 3.7 (SD, 4.73) for Hammersmith Functional Motor Scale–Expanded (HFMSE) score. Notably, by week 52, 3 patients achieved standing with assistance, 1 patient achieved independent standing, and 1 patient achieved walking with assistance.

Top Clinical Takeaways

  • The SMART study underscores the consistent safety profile of onasemnogene abeparvovec (Zolgensma), with manageable transaminase elevations in most patients, irrespective of their weight.
  • A significant proportion of patients maintained or improved motor function, as indicated by measures such as RULM, HFMSE, and achievement of motor milestones, suggesting clinical benefits for heavier patients with SMA.
  • The use of prophylactic prednisolone effectively managed asymptomatic aminotransferase elevation adverse events, supporting the overall tolerability of intravenous onasemnogene abeparvovec in the study.

“The final data from the SMART highlight the safety and efficacy profile of Zolgensma in children with SMA weighing between at least 8.5 kg and less than 21 kg, with a mean age of 4.69 years, most of whom [21 of 24, or 87.5%] had received another disease-modifying therapy and discontinued use by their Zolgensma treatment date,” Sandra P. Reyna, MD, chief scientific advisor and head of global medical engagement for SMA at Novartis, told NeurologyLive®. “The new clinical results supplement emerging real-world experience and use of Zolgensma in countries outside of the US, where authorized use is not restricted by age. The results support the use of Zolgensma in this broader population.”

READ MORE: US National Registry Analysis Reveals Gender Disparities in Pediatric-Onset Facioscapulohumeral Muscular Dystrophy

Presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, by lead author Hugh McMillan, MD, Children’s Hospital of Eastern Ontario, SMART investigated the safety, tolerability and efficacy of a 1-time IV infusion of Zolgensma in pediatric patients who had symptomatic SMA with biallelic mutations in SMN1, any copy number of SMN2, and weighed at least 8.5 kg or less than 21 kg. The study enrolled patients with heterogeneous phenotypes of SMA across the aforementioned 3 weight brackets, ranging in age from approximately 18 months to 9 years. In the trial, 19 patients discontinued prior nusinersen (Spinraza; Biogen), 2 patients discontinued prior risdiplam (Evrysdi; Genentech) and 3 patients were treatment–naïve.

Investigators observed transaminase elevations were ongoing in 14 patients with SMA at the end of study, with no differences observed between weight groups. They noted that all cases of transaminase elevations were reported as asymptomatic and were managed with steroids over a median of 175.0 days. Notably, researchers observed no cases of bilirubin elevations or Hy law among the participants. In 17 patients (70.8%), transient thrombocytopenia reported, and resolved with no reported bleeding events. In addition, 3 patients (13%) had cardiac adverse events (AEs) unrelated to the study treatment. There were no events of thrombotic microangiopathy or dorsal root ganglionopathy reported and the frequency/severity of AEs had similar results across all the weight groups.

All told, all participants had at least 1 treatment-related AE, with 15 (62.5%) who had at least 1 serious AE, 7 (29%) who had SAEs related to Zolgensma, and 20 patients (83.3%) who had aminotransferase elevation AEs. Authors noted that all cases of AEs were asymptomatic and managed with prophylactic prednisolone. Investigators also reported no study withdrawals or deaths occurred in the trial. Overall, researchers noted that the safety profile of Zolgensma observed from the SMART trial is consistent with previously reported results.

“The SMART study was the first Zolgensma open-label clinical study to include older and heavier, as well as previously treated, patients. Zolgensma has already shown a clinical difference in children with SMA under a certain age or weight, and with these results, it confirms the potential this therapy has in a more diverse spectrum of patients,” Reyna said. “We will continue to evaluate the safety and efficacy of Zolgensma in several long-term follow-up studies.”

Click here for more coverage of MDA 2024.

1. McMillan H, Baranello G, Farrar M, et al. Safety and Efficacy of Intravenous Onasemnogene Abeparvovec in Pediatric Patients with Spinal Muscular Atrophy: Findings from the Phase 3b SMART Study. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Poster S110.
2. Novartis presents new data on safety and efficacy of Zolgensma, including maintained and improved motor milestones in older and heavier children with SMA. News Release. Novartis. Published March 4, 2024. Accessed March 6, 2024.
Related Videos
 Kelly Knupp, MD
 Joel Salinas, MD, MBA
Lisa Mosconi, PhD
Emma Ciafaloni, MD, an expert on Duchenne muscular dystrophy
Emma Ciafaloni, MD, an expert on Duchenne muscular dystrophy
© 2024 MJH Life Sciences

All rights reserved.