Real World Safety and exploratory efficacy of gene therapy for patients with 5q-Spinal Muscular Atrophy in a Brazilian cohort

Abstract

Introduction: Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness, ventilatory failure, and reduced survival. Onasemnogene abeparvoves is the first gene replacement therapy (GT) approved to treat this condition. Methods: Observational retrospective study to assess adverse events and efficacy of gene therapy in types 1 and 2 SMA patients through motor milestones and functional motor scales. Results: Forty-one patients with SMA (24 females, 58.5%) were included, including 33 (80.1%) SMA type 1, seven (17.1%) type 2, and one pre-symptomatic. The mean age at GT dosing was 18 (±6.4) months. Thirty-six patients (87.8%) were under previous treatment with nusinersen, and 10 (24.4%) continued nusinersen after GT dosing. Mean CHOP-INTEND increased 13 points after 6 months and 22 points after 12 months of GT (P < 0.001). CHOP-INTEND increase at six months did not differ between groups according to nusinersen maintenance after GT (P = 0.949). Among SMA type 1 patients, 14 (46.6%) reached the ability to sit alone, and three (10%) stood with support. Liver transaminases elevation at least two times higher than the upper limit of normal value occurred in 29 (70.7%) patients. Thrombocytopenia occurred in 13 (31.7%) patients, and one case presented thrombotic microangiopathy. Older age (> two years) was associated with more prolonged use of corticosteroids (P = 0.021). Conclusion: GT is effective in SMA patients, and combined nusinersen after GT does not present additional gain in motor function. Close monitoring of adverse events is necessary, and older age is associated with prolonged corticosteroid use.