Real-World Data for Onasemnogen Abeparvovec (Zolgensma) in Spinal Muscular Atrophy

Background/Purpose: At the time of approval of gene replacement therapy with onasemnogene abeparvovec, limited efficacy and safety data were available in children >8 months, >8.5 kg, and after pretreatment with nusinersen.

Methods: In this study, children with spinal muscular atrophy (SMA) who received gene replacement therapy between 09/2019 and 11/2020 at 18 neuropediatric centers in Germany and Austria were examined according to a standardized protocol over at least 6 months. Motor outcome (CHOP INTEND/HFSME) was analyzed with respect to three age categories (≤8 months, >8 and ≤24 months, >24 months), SMA type, SMN2 copy number, sex, and pretreatment with nusinersen. Furthermore, clinical side effects and laboratory values were evaluated, and the duration and amount of steroid therapy required.

Results: Seventy-six children with SMA (58 pre-treated with nusinersen, 18 treatment-naive) with a median age/weight of 16.8 months (0.8–59 months)/9.1 kg (4.0–15.0 kg) were treated with onasemnogene abeparvovec. CHOP INTEND and HFSME scores improved significantly in 47/59 children. Children pre-treated with nusinersen also significantly improved after switching therapy. Side effects included fever, vomiting, and thrombocytopenia during the first week after gene replacement therapy. Six patients developed (sub)acute liver dysfunction, one of whom with acute liver failure. The increase in liver enzymes correlated with age and weight at the time of therapy, requiring treatment with prednisolone for a median of 15.7 weeks.

Conclusion: SMA patients ≤24 months of age benefit significantly from gene replacement therapy, regardless of pretreatment with nusinersen. Severe side effects may occur and require close follow-up at a specialized center.

Publication History

Article published online:
28 October 2021