New Zolgensma data demonstrate age-appropriate development when used early, real-world benefit in older children, and durability 5+ years post-treatment

Novartis Gene Therapies recently shared new data that reinforce the transformational benefit of Zolgensma (onasemnogene abeparvovec), a one-time treatment for spinal muscular atrophy (SMA). The overall safety profile remains favorable following pre-symptomatic treatment, in the long-term follow-up period from clinical studies and in the real-world setting.

This new data underscore the critical importance of identifying and treating SMA as early as possible. In contrast to the natural history of SMA, which leads to progressive and irreversible loss of motor function, children treated with Zolgensma pre-symptomatically in the Phase 3 SPR1NT trial achieved age-appropriate motor milestones within the World Health Organization (WHO) window of normal development (e.g., sitting, standing and walking) were able to eat exclusively by mouth and did not require ventilatory support of any kind. 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.

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 6 years old and more than 5 years post-treatment.

Emerging findings from the RESTORE registry – designed to provide real-world data for enhancing our understanding of patients cared for in routine practice – indicate 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. Safety events were consistent with the previously described safety profile. Nearly all children with two or more CHOP INTEND assessments available improved or maintained their scores, and most had a clinically meaningful ≥4-point increase.

SPR1NT Data (as of 6/11/20)
SPR1NT is an ongoing Phase 3, open-label, single-arm, multi-center trial designed to evaluate the efficacy and safety of a one-time IV infusion of Zolgensma in pre-symptomatic patients with a genetic diagnosis of SMA and two or three copies of SMN2 who are ≤6 weeks of age. Across the two-copy and three-copy cohorts, all patients (100%) were alive and free of ventilatory support of any kind. All patients (100%) fed orally and did not require feeding tube support of any kind. According to natural history, 60% of two-copy patients would require feeding support by 15 months of age. While all patients experienced at least one adverse event after dosing, there were no serious, treatment-related adverse events. Seven patients were reported to have had serious adverse events, all of which were resolved and were not related to treatment.

Long-Term Follow-Up Studies
After the conclusion of the Phase 1 START study, 10 of 12 patients from cohort 2 (therapeutic dose) voluntarily enrolled in an ongoing observational long-term follow-up study (LT-001). As of the June 11, 2020 data cut, all patients (100%) were alive and free of permanent ventilation. The mean age of patients was 5.2 years (range 4.76.1 years) and the mean time since gene therapy treatment was 5.0 years (range 4.65.6 years). No visits were conducted in LT-001 from December 31, 2019 through June 11, 2020. As of the December 2019 data cut, no previously achieved motor milestones were lost, and two patients (20%) had gained the milestone of standing with assistance (neither of whom had received treatment with nusinersen) during the follow-up period. Six patients (60%) did not require regular, daily respiratory support. Patients from the completed and ongoing Phase 3 IV studies (STR1VE-US, STR1VE-EU, STR1VE-AP, and SPR1NT) and the Phase 1 intrathecal study (STRONG, currently on partial clinical hold) are now enrolling in a long-term follow-up extension study (LT-002).

RESTORE Registry
The RESTORE registry is an ongoing, prospective, multicenter, multinational, observational study of patients with a diagnosis of SMA, including patients from the Zolgensma managed access programs and from partnering clinical sites with a planned follow-up of 15 years. The RESTORE registry provides real-world data for enhancing our understanding of patients with SMA cared for in routine practice. As of December 7, 2020, 70 patients were enrolled who had received Zolgensma when they were 6 months of age or older. Of these, 45 (64 percent) had SMA Type 1.

About Zolgensma® (onasemnogene abeparvovec)
Zolgensma (onasemnogene abeparvovec) is the only gene therapy for SMA and the only SMA treatment designed to directly address the genetic root cause of the disease by replacing the function of the missing or non-working SMN gene to halt disease progression through sustained SMN protein expression with a single, one-time IV infusion.

These data were presented during the 2021 Muscular Dystrophy Association (MDA) Virtual Clinical and Scientific Conference