Real-world experience with switch to onasemnogene abeparvovec after initial therapy with nusinersen or risdiplam

Spinal muscular atrophy is a progressive neurodegenerative disorder leading to motor neuron loss and muscle weakness. In this retrospective single-center study, we evaluated motor and safety outcomes in 40 children (median age, 18 months; range, 5-107; 60% female) with spinal muscular atrophy who received onasemnogene abeparvovec after initial nusinersen (n=38) or risdiplam (n=2) therapy. Motor function was assessed at baseline and at 1 and 6 months post-infusion using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND, n=19) or the Hammersmith Functional Motor Scale Expanded (HFMSE, n=21). Six months after onasemnogene abeparvovec, median scores increased from 27 (range, 18-55) to 37 (range, 20-61) on CHOP-INTEND and from 30 (18-56) to 36 (range, 26-63) on HFMSE (p <0.0001). Clinically meaningful improvement was observed in 67.5% of patients at 1 month and 95.0% at 6 months. All patients experienced transient fever, vomiting, and liver enzyme elevation; thrombocytopenia occurred in 32.5%, with no cases of thrombotic microangiopathy or multi-organ failure. These findings indicate that switching to onasemnogene abeparvovec after prior splicing-modifying therapy yields clinically meaningful motor gains and a manageable safety profile.