Novartis Announces Nature Medicine Publication of Zolgensma Data Demonstrating Age-Appropriate Motor Milestones in Presymptomatic SMA Treatment

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News on June 21, 2022 /BioValleyBIOON/ -- Novartis recently announced that the final results from the completed Phase 3 SPR1NT trial, including both the double-copy and triple-copy cohorts, have been published in the prestigious international medical journal *Nature Medicine*. These data reinforce the transformative benefits of Zolgensma (onasemnogene abeparvovec) as a critical one-time treatment and the only gene therapy for the early treatment of spinal muscular atrophy (SMA).Regardless of whether the SMN2 gene has two or three copies, almost all SMA patients treated with Zolgensma before symptom onsetChildren, they can all achieve motor milestones appropriate for their age, including sitting independently, standing, and walking.

These data stand in stark contrast to the natural history of SMA, a devastating disease that affects approximately 1 in 10,000 infants worldwide. If left untreated,Patients carrying two copies of the SMN2 gene usually develop Type 1 SMA., which leads to progressive and irreversible loss of motor function, and in most cases, death or permanent ventilation by the age of 2.Most children with three copies of the SMN2 gene develop Type 2 SMA., characterized by the inability to walk independently.

Novartis Gene Therapies Chief Medical Officer Shephard Mpofu, M.D., stated: "The robust data from both the bi-copy and tri-copy cohorts of the SPR1NT trial are being released simultaneously for the first time, further supporting the significant and clinically meaningful benefits of Zolgensma for pre-symptomatic SMA infants. When treated with Zolgensma before symptom onset, all 29 patients in the SPR1NT trial not only survived but also thrived—breathing and feeding independently, with most even able to sit, stand, and walk without assistance."

Spinal Muscular Atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness, paralysis, and even death. Without treatment, most children with severe SMA can only survive on permanent mechanical ventilation by the age of 2 or face eventual death.Zolgensma is so far the only approved treatment for SMA patients (including inDiagnosisThe first and only gene therapy for patients who have not yet shown symptoms. Zolgensma addresses the genetic root cause of SMA by providing a functional copy of the human SMN gene, and its sustained expression of SMN protein, delivered through a single intravenous injection, halts disease progression.

Results from the SPR1NT study are as follows:

——In the dual-copy queue,All children (100%) treated pre-symptomatically reached the primary endpoint of sitting independently for ≥30 seconds., including 11/14 (79%) of patients achieving this milestone within the World Health Organization (WHO) normal development window. The majority of patients continued to stand independently (11/14) and walk independently (9/14), with most falling within the typical range of normal development.

——In the three-copy cohort, 14/15 (93%) of children continued to walk independently, with most (11/15, 73%) achieving this milestone within the WHO's normal developmental window. All 15 children (100%) reached the primary endpoint of standing independently for ≥3 seconds, including 14/15 (93%) achieving this milestone within the WHO's normal developmental window.

——The reported adverse reactions are consistent with previous data, and no new safety signals have been identified. Patients in the SPR1NT study have been invited to participate in a long-term follow-up study to collect additional safety and efficacy data. Updated data assessing improvements in motor function will be announced later this year.

SMA is a rare hereditary neuromuscular disease caused by the lack of a functional SMN1 gene. SMA can lead to the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing, and basic movement.

SMN2 is a backup gene of SMN1, and the two are almost identical. The number of SMN2 copies is negatively correlated with the severity of the SMA phenotype. Patients with two copies of the SMN2 gene may develop infantile SMA (also known as Type 1 SMA); while patients with three or four copies of the SMN2 gene may develop later-onset SMA (Type 2 SMA and Type 3 SMA). SMA is the leading genetic killer in children under 2 years old, with Type 1 SMA being the most common type, accounting for about 60% of all cases. Without treatment, more than 90% of patients will die or require permanent ventilation by the age of 2.

Zolgensma is a revolutionary and highly innovative one-time gene therapy designed to address the genetic root cause of SMA by replacing the function of the missing or non-working SMN1 gene.After a single intravenous (IV) infusion, Zolgensma introduces a functional copy of the SMN1 gene into the patient’s cells, continuously expressing functional SMN protein to halt disease progression, thereby providing long-term improvement in patient quality of life.

Clinical studies have shown that,In symptomatic and pre-symptomatic SMA patients, a single infusion of Zolgensma demonstrated significant clinical benefits, including extended event-free survival and the achievement of motor milestones not seen in the natural history of the disease.(Bioon.com)

Source of Original Text:Novartis announces Nature Medicine publication of Zolgensma data demonstrating age-appropriate milestones when treating children with SMA presymptomatically