15.33 AVXS-101 in presymptomatic spinal muscular atrophy (SMA)

BackgroundOnasemnogene abeparvovec (AVXS-101) is a gene-replacement therapy that treats the genetic root cause of SMA, biallelic survival motor neuron 1 gene (SMN1) deletion/mutation. In a phase 1 study, AVXS-101 improved survival and motor function of symptomatic SMA type 1 patients. In SPR1NT (NCT03505099), AVXS-101 is being evaluated in presymptomatic newborns with SMA.MethodsSPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2xSMN2or 3xSMN2. Asymptomatic infants aged ≤6 weeks receive a one-time, intravenous AVXS-101 infusion. Safety and efficacy are assessed through 18 or 24 months for patients with 2x or 3xSMN2, respectively. Primary outcomes are independent sitting ≥30 seconds (2xSMN2) or assisted standing (3xSMN2).ResultsAs of 8 March 2019, 18 infants aged 8–40 days received AVXS-101 (11 female; 8 with 2xSMN2; 9 with 3xSMN2; 1 with 4xSMN2). Among patients with 2xSMN2, mean CHOP-INTEND at baseline was 44.0 points, which increased by 14.4 points at 3 months (n=7); 6/8 patients scored ≥60 points; 3/8 reached maximum score. 4/8 patients sat unassisted; all ages of sitting milestone achievements were within the WHO range (1st–99th percentile: 3.8–9.2 months).ConclusionsPreliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.