SMA CLINICAL DATA, OUTCOME MEASURES AND REGISTRIES: P.96Number needed to treat in spinal muscular atrophy type 1 with AVXS-101 relative to nusinersen

Abstract

Spinal muscular atrophy (SMA) is a rare genetic and life-threatening neuromuscular disease. This study assessed the number needed to treat (NNT) to prevent death and use of permanent assisted ventilation and improve motor function with AVXS-101 compared to nusinersen in patients with SMA type 1 (SMA1). Patients diagnosed with SMA1 were treated in clinical trials with AVXS-101 (NCT02122952; study cohort 2; N=12) or nusinersen (NCT02193074; N=80). Trial duration was up to 24 months for AVXS-101 (median = 24.1 months) and up to 13 months for nusinersen (median = 9.2 months). NNT with AVXS-101 compared to nusinersen was assessed for survival and event-free survival (absence of death and use of permanent assisted ventilation) at last visit, and for motor function (increase of ≥4 points in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP-INTEND] score from baseline) at last visit and at a median of 9 months. For the nusinersen trial, CHOP-INTEND score was measured for patients with ≥6 months of follow-up (N=73). The NNT to prevent one death, one event (death or use of permanent assisted ventilation), or for one patient to improve motor function relative to nusinersen was calculated as the reciprocal of the difference between AVXS-101 and nusinersen in event rates or motor function achievement rates. Patient mean age at first dose was 3.4 (0.9-7.9) and 5.3 (1.7-7.9) months in the AVXS-101 and nusinersen trials. NNT analyses suggests that treating 6.2 patients with AVXS-101 instead of nusinersen would prevent 1 more death by the last visit; treating 2.6 patients with AVXS-101 versus nusinersen would prevent 1 more event; and treating 3.5 patients with AVXS-101 versus nusinersen would allow 1 more patient to improve motor function (at last visit and at a median of 9 months). Efficacy in preventing death and use of permanent assisted ventilation and in improving motor function is much higher with AVXS-101 versus nusinersen.