A potential gene therapy for spinal muscular atrophy

BASEL, Switzerland—Novartis has announced new data that reinforces the transformational benefit of Zolgensma (onasemnogene abeparvovec), a one-time treatment for spinal muscular atrophy (SMA). The overall safety profile remains favorable following presymptomatic treatment, according to results from the long-term follow-up period from clinical studies and in the real-world setting. These data were presented during the 2021 Muscular Dystrophy Association (MDA) Virtual Clinical and Scientific Conference.

According to the company, the new data underscore the critical importance of identifying and treating SMA as early as possible. In contrast to the natural history of this disease, which leads to progressive and irreversible loss of motor function, children treated with Zolgensma presymptomatically in the Phase 3 SPR1NT trial achieved age-appropriate motor milestones within the World Health Organization (WHO) window of normal development and ate exclusively by mouth. 

There were no serious, treatment-related adverse events reported in SPR1NT. In addition, children identified via newborn screening enrolled in the RESTORE real-world registry were significantly less likely to receive more than one SMA therapy compared with those who were diagnosed clinically.

“Without the benefit of disease-modifying therapy, newborns with biallelic SMN1 deletions and two or three copies of SMN2 would normally develop SMA type 1 and SMA type 2, respectively. When treated with Zolgensma prior to the onset of symptoms, children in the SPR1NT trial achieved milestones like sitting, standing, and walking at an appropriate age, grew as expected without nutritional assistance, and remained free of all forms of mechanical ventilatory support,” said Kevin Strauss, medical director of the Clinic for Special Children in Pennsylvania. “This stands in sharp contrast to the natural progression of SMA type 1, which would otherwise render them helpless within the first year of life and unable to swallow, breathe, or survive without mechanical support. The transformative benefit of early intervention, as seen in SPR1NT, further underscores the urgent need for newborn screening.”

Long-term follow-up data from two studies continued to demonstrate that children treated with Zolgensma experienced a sustained benefit from gene therapy in the years following dosing, with no evidence of new or delayed safety signals. Zolgensma led to achievement of new milestones years after treatment—including sitting—with sustained durability in children now up to six years old and more than five years post-treatment.

Emerging findings from the RESTORE registry, which was designed to provide real-world data for enhancing understanding of patients cared for in routine practice, indicate that older children (≥6 months) achieved a clinically meaningful benefit when treated with Zolgensma alone, after switching to gene therapy or in combination with another SMA therapy, with safety events consistent with the previously described safety profile. 

Shephard Mpofu, chief medical officer of Novartis Gene Therapies concluded, “With more than 1,000 patients now treated, these data presented at MDA further reinforce what we’ve come to expect from Zolgensma—consistent, significant and clinically meaningful therapeutic benefit in SMA, including prolonged event-free survival, achievement of motor milestones unseen in natural history of the disease, and durability now more than five years post-dosing.”