SMA causes loss of motor/respiratory function due to survival motor neuron 1 (SMN1) deletion/mutation. Copies of SMN2 modify disease severity. A range of phenotypes may occur with 3SMN2 with approximately 85% developing symptoms in infancy and not being able to walk independently without intervention.
Evaluate the safety/efficacy of onasemnogene abeparvovec (formerly AVXS-101) in presymptomatic SMA patients with 3 copies of the SMN2 gene.
SPR1NT (NCT03505099) is an ongoing multicenter, open-label, Phase III study. Asymptomatic patients expected to develop SMA (Cohort 2: 3SMN2, ≤6 weeks) received a one-time intravenous infusion and are assessed through 24 months. Primary outcome: standing unassisted for ≥3 seconds. Secondary outcome: independent walking. Safety outcomes: incidence of adverse events (AEs)/serious AEs.
As of 11 June 2020, 15 patients in Cohort 2 were enrolled (enrollment complete). Median age (range) at last visit (months): 15.2 (3.3–21.1); median follow-up time (range) at last visit (months): 14.5 (2.0–19.9). All patients are alive and none used ventilatory or feeding tube support at any time. Eight of 15 Cohort 2 patients had achieved the primary efficacy endpoint of stands alone within the normal developmental window (16.9 months, De Onis 2006).The remaining 7 patients were all younger than 16.9 months of age. Six patients also walked alone within the normal developmental window (17.6 months, De Onis 2006); remaining patients were younger than 17.6 months of age. 15/15 patients experienced ≥1 AE (120 total AEs); 7/15 experienced treatment-related AEs (26 total AEs). 2/15 experienced a serious AE (2 total AEs) but both serious AEs resolved and were considered unrelated to treatment. No AEs caused study discontinuation or death.
Patients in this cohort treated with onasemnogene abeparvovec have achieved gross motor milestones similar to non-SMA, typically developing peers, demonstrating a significant therapeutic benefit. Study is ongoing.