Novartis Gene Therapies today announced new interim data from the ongoing Phase 3 STR1VE-EU clinical trial for Zolgensma® (onasemnogene abeparvovec). The data demonstrates that patients with spinal muscular atrophy (SMA) Type 1 continued to experience significant therapeutic benefit, including event-free survival, rapid and sustained improvement in motor function, and motor milestone achievement, including for some patients with more aggressive disease at baseline compared to previous trials. This represents data as of December 31, 2019, and was presented today during a virtual Clinical Trial Poster Session as part of the World Muscle Society (WMS) 2020 Virtual Congress. The data further supports the robust clinical evidence that has demonstrated a consistent, transformative benefit across Zolgensma clinical trials for the treatment of patients with SMA.

Phase 3 STR1VE-EU Data as of December 31, 2019
STR1VE-EU is designed to evaluate the efficacy and safety of a single, one-time IV infusion of Zolgensma in patients with SMA Type 1 who are less than 6 months of age at the time of gene therapy, with one or two copies of the SMN2 backup gene and who have bi-allelic SMN1 gene deletion or point mutations. The mean age of dosing was 4.1 months and the mean age at the onset of symptoms was 1.6 months.

At last visit before the data cutoff, patients in STR1VE-EU were between 6.9 and 18.6 months of age, and mean duration in the study was 10.6 (1.8–15.4) months. Thirty-one out of 32 (97%) patients in the intent-to-treat (ITT) population survived event-free, including 30 (93.8%) who could have reached 10.5 months of age and 18 (56.3%) who could have reached 13.6 months of age. An event is defined as the need for tracheostomy or the requirement of ≥16 hours of respiratory assistance per day (via non-invasive ventilatory support) for ≥14 consecutive days in the absence of an acute reversible illness, excluding peri-operative ventilation.

Twenty-one patients (65.6%) achieved motor milestones not observed in the natural history of SMA Type 1. This includes six patients (18.8%) who could sit independently for ≥10 seconds (the primary efficacy endpoint), 20 patients (66.7%) who gained head control, eight patients (25%) who were able to roll from back to sides and one patient who could stand with assistance, crawl and walk with assistance.

The majority (91.7%) of patients who were free of ventilatory support at baseline remained either completely free of ventilatory support or received prophylactic BiPAP support during the study for acute reasons. Two-thirds (66.7%) of patients in the ITT population were able to feed orally without the need for feeding support, an important indicator of stabilization/halting of disease progression.

As previously reported, one patient discontinued the study because of a serious adverse event of hypoxic-ischemic brain damage and respiratory distress that resulted in death. Novartis and the investigator considered the events and death to be unrelated to treatment with Zolgensma based on autopsy findings. Thirty-two of 33 patients were reported to have at least one adverse event (AE), of which six patients experienced serious adverse events that were considered by the investigator to be related to Zolgensma. Liver transaminase elevations, some of which were reported as adverse events, were experienced by 29 of 33 patients (87.9%), but all resolved with the use of prednisolone. Four patients had reported decreases in platelet counts <75,000, three of which were isolated laboratory abnormalities without adverse events reported. Overall, no new safety signals have been identified and the reported adverse events are consistent with the cumulative safety profile with Zolgensma.

Novartis Gene Therapies is grateful to the courageous patients and families who participate in clinical trials, enabling the company to further its efforts to make a meaningful difference in the lives of patients with rare genetic diseases.