MDA 2025: SMA kids maintaining Zolgensma benefits 10 years later
Long-term trial data show children retain motor milestones up to a decade
Children with spinal muscular atrophy (SMA) given the gene therapy Zolgensma (onasemnogene abeparvovec-xioi) in infancy are maintaining motor milestones after up to a decade of follow-up, according to new long-term clinical trial data.
“At their last assessment, … patients [given the now-approved dosage of Zolgensma] were able to demonstrate the highest milestone demonstrated at their first assessment,” the researchers wrote, adding that “two patients … newly achieved standing with assistance.”
These data were shared at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, ongoing in Dallas and virtually.
The findings, from a follow-up study that’s now spanned 10 years from the first trial, were presented in a poster titled “Long-term Follow-up of Onasemnogene Abeparvovec Gene Therapy for Patients with Spinal Muscular Atrophy Type 1 from the START Trial.” The research was funded by Novartis, which sells Zolgensma.
According to the researchers, “there were no reports” of severe adverse events, or side effects, among the children still in the study.
5 children with SMA type 1 given Zolgensma can stand, 2 can walk
SMA is chiefly caused by mutations in the gene SMN1. A one-time treatment, Zolgensma is designed to deliver a healthy version of this gene to the body’s cells.
The gene therapy is approved in the U.S. to treat SMA patients younger than 2, and is now available in more than 50 countries worldwide, according to Novartis.
The first clinical trial testing Zolgensma, launched in 2014, was called START (NCT02122952). It tested the intravenous, or into-the-vein, therapy in 15 babies with SMA type 1 — the most common, and one of the most severe forms of the disease. All of the children had already begun experiencing symptoms by the time they received gene therapy.
After the START study ended, 13 of the children continued to be followed as part of a long-term study called LT-001 (NCT03421977), which is still underway and slated to run through 2030. Three of these children had been given a low dose of Zolgensma; the other 10 got a higher dose — the one that is now approved. Since receiving the gene therapy, most of the children have also started add-on treatment with the SMA therapies Spinraza (nusinersen) or Evrysdi (risdiplam).
As of the latest follow-up, on July 1, 2024, all low-dose and five of the therapeutic dose patients were still in the study. Reasons for discontinuing among the other five children included failure to follow-up and no longer having consent from a parent or legal guardian.
A single intravenous infusion of [Zolgensma] continued to demonstrate a favorable benefit-risk profile and durable efficacy up to 10 years after dosing.
“All patients survived,” the researchers wrote in the study abstract being presented at the MDA Conference. The team also noted that “all patients were free of permanent ventilation except one [given the therapy’s lower dose in the trial].”
The three children given that low dose had been followed for about 10 years on average by the latest follow-up. All used a feeding tube. One of these children was able to sit with support; the other two had not achieved any motor milestones usually seen typically developing youngsters, the team noted.
For the children given the therapeutic dose of Zolgensma, the average follow-up time was now more than nine years. All of these children were still alive without the need for permanent ventilation; six of them used a feeding tube while the other four did not.
All of these patients were able to sit without support. Further, five were able to stand with assistance, and two were able to walk unassisted. At their most recent assessment, all of the patients retained the highest motor milestones that they’d achieved in the parent START trial.
As for safety, none of the adverse events deemed of special interest were considered to be related to Zolgensma treatment by the study investigators. The most frequent serious side effects seen were acute respiratory failure, dehydration, and pneumonia. However, the investigators noted that such side effects “are common in children with SMA because of the underlying disease process.”
Overall, according to the researchers, “a single intravenous infusion of [Zolgensma] continued to demonstrate a favorable benefit-risk profile and durable efficacy up to 10 years after dosing.”
Note: The SMA News Today team is providing live coverage of the 2025 MDA Clinical & Scientific Conference March 16-19 in Dallas. Go here to see the latest stories from the conference.
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