Spinal muscular atrophy (SMA) occurs due to a mutation in the SMN1 gene. It most typically has an onset in early childhood and presents as impairment in motor, bulbar, and respiratory function. In a symposium at the European Paediatric Neurology Society’s (EPNS) 2023 congress, three leading experts in SMA discussed the findings of real-world evidence (RWE) studies of the first gene therapy approved in NMD, in 2019 in the USA, and 2020 in Europe. Onasemnogene abeparvovec combines an adeno-associated virus (AAV9) vector with a functional copy of SMN complementary DNA, and is delivered in a single infusion. While clinical trials of onasemnogene abeparvovec show its efficacy and safety in populations with SMA who are symptomatic and pre-symptomatic, RWE studies have expanded the understanding of this therapy to wider SMA patient groups in the real-world clinical practice setting. Combined, such studies show how administration of onasemnogene abeparvovec in patients with symptomatic SMA can lead to motor and respiratory function improvement or stabilisation and achievement of motor milestones in naïve or pre-treated patients, while in patients who are pre-symptomatic, administration may lead to a normal development. The experts also discussed how understanding the benefit/risk profile of this gene therapy can help with decision-making over its use in patients with SMA. They highlighted how onasemnogene abeparvovec efficacy and safety can be affected by clinical status, disease severity, weight, age, and previous treatment at the time of infusion. Recently published RWE points to improvements being best predicted by baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score and age at treatment initiation, and in regard to safety and tolerability profile, liver enzyme elevation is the most predominant treatment-emergent adverse event (TEAE) with onasemnogene abeparvovec; hence, a prednisolone (or equivalent) dosing regimen is administered prior to, during, and for at least 3 months following infusion. The experts discussed how careful monitoring and adequate multidisciplinary team discussion, including colleagues from other specialities, such as hepatologists and paediatric immunologists, is advised in all cases of SMA receiving an onasemnogene abeparvovec infusion.
