Presymptomatic SMA Treatment With Zolgensma Associated With Normal Development


New data presented at MDA 2022 showcased positive motor and bulbar function data.

Pediatric patients with spinal muscular atrophy (SMA) treated presymptomatically with onasemnogene abeparvovec (Zolgensma; Novartis) continue to demonstrate age-appropriate development, according to new data from the phase 3 SPR1NT study (NCT03505099).

These data were presented at the 2022 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 13-16, in Nashville, Tennessee.

“Results from SPR1NT again confirm the remarkable impact of Zolgensma for children at risk for SMA who are treated before the onset of symptoms. In sharp contrast to the natural course of SMA, children treated preemptively with Zolgensma are standing and walking, with few or no signs of neuromuscular disease. Many of these children achieve patterns of motor development indistinguishable from their healthy peers without SMA,” Kevin Strauss, MD, medical director, Clinic for Special Children, Pennsylvania, said in a statement. “These data clearly demonstrate the value of newborn screening for SMA, which is vital to affording children the earliest diagnosis and treatment to ensure the best possible outcomes.”

The phase 3, open-label, SPR1NT trial evaluated presymptomatic= treatment of patients with SMA with either 2 or 3 copies of SMN2 less than 6 weeks of age. New data reported is from the 3-copy cohort, who had a mean age of dosing of 28.7 days (range, 9-43). Most patients with 3 copies of the gene develop SMA type 2.

READ MORE: Gene Therapy Updates in Neuromuscular Diseases

Investigators found that almost all treated children (n = 14/15; 93%) with 3 copies of the SMN2 back-up gene developed independent walking skills and 11 (73%) developed this skill within the World Health Organization (WHO) window of normal development, differing from natural history. The study met its primary endpoint, and all children were able to stand alone for at least 3 seconds, most (n = 14) within the WHO window of normal development.

No patients required nutritional and respiratory support during the study. There were no serious, treatment-related adverse events (AEs) but 3 patients did experience unrelated serious AEs. All patients experienced at least 1 AE after dosing and 8 (53%) were treatment-related.

Novartis also presented descriptive post-hoc analyses of the START (NCT02122952), STR1VE-EU (NCT03461289), and STR1VE-US (NCT03306277) trials, with data from 65 treated children. Altogether, investigators found that of 20 evaluable, treated children with SMA type 1 from the studies, 16 of 20 (80%) achieved the bulbar function endpoint, a composite score of communication, swallowing, and maintenance of airway protection.

Specifically, 19 of 20 evaluable patients (95%) met the communication endpoint, 60 of 65 evaluable patients (92%) met the swallowing endpoint, and 60 of 65 evaluable patients (92%) were able to maintain airway protection.

“The effect of SMA Type 1 on bulbar function often leads to debilitating complications, such as increased risk of aspiration, as well as social consequences from impairment of speech development. These post-hoc data suggest Zolgensma can have an important impact on a child’s well-being,” Shephard Mpofu, MD, senior vice president and chief medical officer, Novartis Gene Therapies, added to the statement. “Additional data presented at MDA continue to reinforce the consistent, significant and clinically meaningful therapeutic benefit of Zolgensma in the real-world setting, including in patients outside of our current clinical trial experience.”

Novartis data again demonstrate age-appropriate development when Zolgensma is used presymptomatically, and post-hoc data reveal SMA Type 1 patients could speak, swallow and maintain airway protection. News release. Novartis. March 14, 2022.
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