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

Abstract

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. An observational retrospective study was conducted to assess adverse events and efficacy of GT in SMA patients. Forty-one patients with SMA (24 females, 58.5% and 33 SMA type 1, 80.1%) were included. 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. Mean CHOP-INTEND increased 13 points after 6 months and this finding 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. 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 presented thrombotic microangiopathy. Older age (> 2 years) was associated with more prolonged use of corticosteroids (p = 0.021). GT is effective in SMA patients, combined nusinersen after GT does not present additional gain in motor function, and older age is associated with prolonged corticosteroid use.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy

“…These real-world studies have confirmed the efficacy of the gene replacement therapy in an expanded age range of patients eligible for treatment, including those up to two years old and also patients with three copies of SMN2 , regardless of the type of SMA. 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 Additionally, some studies have evaluated the use of onasemnogene abeparvovec in patients who had previously been treated with other specific therapies, such as nusinersen or risdiplam. 102 103 105 106 108 …”

“… 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 Additionally, some studies have evaluated the use of onasemnogene abeparvovec in patients who had previously been treated with other specific therapies, such as nusinersen or risdiplam. 102 103 105 106 108 …”