AveXis, a Novartis company, announced a one-time infusion of Zolgensma® (onasemnogene abeparvovec-xioi) showed rapid, significant, and clinically meaningful therapeutic benefit in patients with spinal muscular atrophy (SMA) across a range of studies, including in patients treated pre-symptomatically, and sustained durability in patients now up to 5 years post-dosing and some patients more than 5 years of age.

Interim data from the ongoing SPR1NT study continue to show patients achieved age-appropriate motor milestones when treated with Zolgensma pre-symptomatically. Most patients (7/8) with two copies of SMN2 who achieved the ability to sit independently did so within the World Health Organization (WHO) window of normal development. The six remaining patients in this cohort of 14 patients have not yet passed the developmental window. The importance of independent sitting is that it allows for the potential development and integration of the cognitive, sensory, and motor skills that are important for functional independence and social development. Additionally, nearly all patients were fed orally and required no feeding support. Most remained within the age-appropriate weight range. No patients required ventilatory support of any kind.

SMA Type 1 patients experienced rapid, sustained, and clinically meaningful improvements in motor function in the completed pivotal STR1VE-US study. In STR1VE-US, nearly all (91%) patients met the co-primary efficacy endpoint of event-free survival at 14 months, and more than half (59%) of patients met the co-primary efficacy endpoint of sitting for ≥30 seconds at 18 months of age, a milestone never achieved in the natural history of SMA Type 1. Importantly, nine of 22 patients demonstrated the “ability to thrive” at 18 months of age. As the goal of treatment for SMA Type 1 moves beyond survival and motor milestone achievement, the STR1VE-US trial is the first to incorporate this stringent composite endpoint—inclusive of functions of swallowing, feeding, and age-appropriate weight maintenance—and demonstrate remarkable achievements in symptomatic patients with SMA Type 1, the most prevalent form of the disease accounting for 60% of SMA diagnoses.

New data from the START long-term, follow-up study continue to demonstrate the durability of a single, one-time dose of Zolgensma in patients now up to five years post-dosing and some patients more than 5 years of age. All patients in this study who received the therapeutic dose were alive and free of permanent ventilation and continued to maintain developmental milestones, including two patients who achieved the new milestone of standing with assistance during the long-term follow-up period.

Cumulative safety data from patients treated with intravenous Zolgensma in clinical trials, U.S. managed access program, the RESTORE global registry and commercial experience were consistent with previously reported safety information. Reported adverse events (AEs) were monitorable and manageable, and the overall benefit-risk safety profile remains favorable.

Please see the complete press release from AveXis with full study details and results as of December 31, 2019.

Cumulative Safety Data (as of December 31, 2019)

Safety data from post-marketing experience (192 patients) was consistent with previously observed safety data across all clinical investigations of IV Zolgensma (100 patients) and the U.S. managed access program, as well as the RESTORE global patient registry (43 patients). Data reviewed from 335 patients indicated that nearly all patients experienced AEs; however, most were not serious and were unrelated to treatment. In general, AEs associated with Zolgensma are monitorable and manageable: (1) liver transaminase elevations should be monitored through liver function tests and managed through the use of prophylactic prednisolone; (2) thrombocytopenia events have been transient and resolved without medical intervention and can be monitored through platelet counts; and (3) reported cardiac events have been heart rate changes and laboratory abnormalities without associated clinical sequelae. Troponin I should be monitored.

A thorough analysis has been completed to assess sensory abnormalities indicative of dorsal root ganglia inflammation. While this remains a preclinical finding and clinical events have not been reported, AveXis has implemented a monitoring plan in clinical trials to evaluate and characterize this further.

No new deaths reported; two deaths were previously reported after Zolgensma dosing (STR1VE-US and STR1VE-EU), both of which were considered unrelated to treatment based on autopsy findings.