Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial

Abstract

Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT (NCT03505099), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset, all stood independently before 24 months (P < 0.0001; 14 within normal developmental window), and 14 walked independently (P < 0.0001; 11 within normal developmental window). All survived without permanent ventilation at 14 months; ten (67%) maintained body weight (≥3rd WHO percentile) without feeding support through 24 months; and none required nutritional or respiratory support. No serious adverse events were considered treatment-related by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.

Modelling the Cost-Effectiveness and Budget Impact of a Newborn Screening Program for Spinal Muscular Atrophy and Severe Combined Immunodeficiency

“…The following supporting information can be downloaded at: , Table S1: Model parameter and expected values with ranges for the model. References [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] are cited in the Supplementary Materials.…”

Onasemnogene Abeparvovec: A Review in Spinal Muscular Atrophy

“…The SPR1NT trial enrolled infants aged ≤ 6 weeks with pre-symptomatic SMA and two [21] or three [22] copies of SMN2 (with no c.859C→G modifier variants). Participants were able to swallow and breathe normally and had no clinical evidence of neuromuscular disease [21,22].…”

“…The SPR1NT trial enrolled infants aged ≤ 6 weeks with pre-symptomatic SMA and two [21] or three [22] copies of SMN2 (with no c.859C→G modifier variants). Participants were able to swallow and breathe normally and had no clinical evidence of neuromuscular disease [21,22]. All children received a single intravenous infusion of onasemnogene abeparvovec 1.1 × 10 14 vg/kg at the median age of 21 days in the two-copy cohort [21] and 32 days in the three-copy cohort [22].…”

“…Participants were able to swallow and breathe normally and had no clinical evidence of neuromuscular disease [21,22]. All children received a single intravenous infusion of onasemnogene abeparvovec 1.1 × 10 14 vg/kg at the median age of 21 days in the two-copy cohort [21] and 32 days in the three-copy cohort [22]. The primary endpoints were independent sitting for ≥ 30 s at any visit up to 18 months of age (two-copy cohort) [21] and independent standing, confirmed by independent video review, for ≥ 3 s at any visit up to 24 months of age (three-copy cohort) [22].…”

New drug: Onasemnogene abeparvovec for spinal muscular atrophy

“…4 The 15 children with three copies of SMN2 were all able to stand for at least three seconds at the age of two years and 14 were able to walk. 4,5 Adverse reactions to onasemnogene abeparvovec are common. A review of safety data from several trials identified hepatotoxicity, thrombocytopenia, and cardiac adverse events as potential problems.…”