SMA causes loss of motor/respiratory function due to survival motor neuron 1 (SMN1) deletion/mutation. Copies of SMN2 modify disease severity. Approximately 97% of patients born with 2 copies of SMN2 develop infantile-onset SMA type 1. If untreated, median survival is 13.6 months and patients do not sit without support.
Evaluate the safety/efficacy of onasemnogene abeparvovec (formerly AVXS-101) in presymptomatic SMA patients with 2 copies of the SMN2 gene.
SPR1NT (NCT03505099) is an ongoing multicenter, open-label, Phase III study. Asymptomatic patients expected to develop SMA (Cohort 1: 2SMN2, ≤6 weeks) received a one-time intravenous infusion and are assessed through 18 months. Primary outcomes: sitting for ≥30 seconds. Secondary outcomes: survival and independent feeding with normal weight. Exploratory outcome: motor function improvement (CHOP INTEND). Safety outcomes: incidence of adverse events (AEs)/serious AEs.
As of 11 June 2020, 14 patients in Cohort 1 (2SMN2) were enrolled (enrollment complete). Median age (range) at last visit (months): 15.60 (8.8–18.8); median follow-up time (range) at last visit (months): 14.85 (8.0–18.4). All patients are alive and did not use ventilatory or feeding tube support as of last visit. 11 patients had achieved the primary endpoint of sitting without support for ≥30 seconds; 10/11 were within the normal development window (9.2 months, De Onis 2006) and similar to non-SMA, typically-developing peers; all achieved CHOP INTEND scores of ≥50. 14/14 patients experienced ≥1 AE (131 total AEs); 10/14 experienced treatment-related AEs (22 total AEs). 5/14 experienced a serious AE (7 total AEs) but all serious AEs resolved and were treatment-unrelated. No AEs caused study discontinuation/death.
Overall, 79% of patients in this cohort achieved the primary endpoint as of the data-cut, at an age similar to non-SMA typically developing children, and children with some delay, demonstrating a significant therapeutic benefit. Study is ongoing.