Phase 3 Data Show Success in Treating Children with Spinal Muscular Atrophy

Novartis just released results from the phase 3 SPR1NT study that evaluated the safety and efficacy of a one-time intravenous infusion of onasemnogene abeparvovec (Zolgensma). The trial included children who were 6 weeks old or younger, presymptomatic with a genetic diagnosis of spinal muscular atrophy (SMA) and 2 or 3 copies of SMN2.

According to the statement, children with 3 copies of the SMN2 back-up gene who received the treatment achieved age-appropriate motor milestones like standing and walking. After treatment, the children didn’t require ventilatory or feeding tube support and no serious, treatment-related adverse events occurred.

Post-hoc analyses showed children with type 1 spinal muscular atrophy were able to gain or maintain important measures of bulbar function after being treated with onasemnogene abeparvovec. These functions included the ability to speak, swallow and meet nutritional needs, and 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, SVP, Chief Medical Officer, Novartis Gene Therapies said in a statement. “Additional data presented at [Muscular Dystrophy Association] 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.”

Most children with 3 copies of the SMN2 back-up gene develop spinal muscular atrophy type 2 if they don’t get treatment. Patients with SMA type 2 are incapable of walking independently. However, 93% of children in the 3-copy cohort of the trial were able to and most of them (73%) were within the window of normal development according to the World Health Organization (WHO).

Spinal muscular atrophy is a rare, genetic neuromuscular disease and one of the leading genetic causes of infant death. The condition is a result of a lack of a functional SMN1 gene. In patients with severe forms, a decline in motor neurons is usually rapid and irreversible, debilitating muscle functions like breathing, swallowing and basic movement.

Within the 3-copy cohort, 100% of patients met the primary endpoint of standing unassisted for at least 3 seconds by 24 months of age, 93% walked independently, and all patients were able to complete the entire trial period without any nutritional or respiratory support.

After dosing, at least 1 adverse event was experienced by each patient with 8 of them being treatment-related. However, there were no serious treatment-related adverse events. Of the 15 patients, 3 experienced serious adverse events which were resolved.

“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 in 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.”