Onasemnogene Abeparvovec in Patients With SMA : Interim Results of the RESTORE Registry in Japan

Objective There are limited real‐world data regarding the safety and effectiveness of onasemnogene abeparvovec (OA; Zolgensma) infusion, a one‐time gene replacement therapy, for Japanese patients with spinal muscular atrophy (SMA). We aimed to improve understanding of the real‐world outcomes for OA in Japan. Methods We report interim, 5‐year results of Japanese post‐marketing surveillance of OA (part of the RESTORE registry: NCT04174157). Results Eighty patients were registered and treated with OA (monotherapy: 30%; bridge or switch to OA: 54%). The median (min, max) age (months) was 3.0 (0, 18) at symptom onset and 10.0 (0, 24) at OA infusion. Forty patients each (50.0%) had two or three survival motor neuron 2 ( SMN2 ) gene copies. Ten patients were identified by newborn screening. Adverse events related to OA were reported in 98.8% (serious: 26.3%; no deaths). Adverse events of special interest occurred in 92.5%, including hepatotoxicity (90.0%), transient thrombocytopenia (62.5%), cardiac adverse events (33.8%), and thrombotic microangiopathy (5.0%). Event‐free survival at 3 years since OA administration was 93.0%. There was one death from disease progression. Of 39 patients with two or more developmental milestones, 64.1% achieved new developmental milestones and 15.4% maintained their milestones. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores increased by ≥ 4 points in 81.8% (54/66). Interpretation The safety profile of OA in Japanese patients with SMA mirrored that of earlier studies. In our real‐world observations, patients showed gains in or maintenance of motor milestones or motor function scores that were sustained over the observation period. Trial Registration NCT04174157 ( ClinicalTrials.gov )