Therapeutic Efficacy and Safety of onasemnogene abeparvovec Gene Therapy for Spinal Muscular Atrophy Type 1: Updated Systematic Review with Meta-Analysis

Objectives: The objective of this study is to conduct a meta-analysis to evaluate the efficacy and safety of onasemnogene abeparvovec (OA). Background: Onasemnogene abeparvovec is a gene therapy approved from the U.S. Food and Drug Administration in May 2019. Unlike other therapies, it offers unique benefit of a single-time dose administration. The therapy has since been approved for the treatment of SMA1 patients in multiple countries. Given its increasing global use, an updated systematic analysis is warranted to comprehensively assess its safety and clinical efficacy. Methods: An electronic literature search was done across PubMed, Scopus and WOS databases until October 2025. We conducted a meta-analysis of single-arm studies investigating the effects of onasemnogene therapy on safety and efficacy outcomes. Safety outcomes include overall, serious and drug related adverse events while efficacy outcomes include overall and event-free survival and change from baseline in CHOP-INTEND score. Effect estimates were presented in random effect model as single proportions for dichotomous data and pooled mean change from baseline for continuous data with and 95% confidence intervals (CI) for both. Results: Overall, twenty-one studies were included with total of 565 SMA1 patients. The pooled percentage of overall survival was 98% [95% CI: 96:99]. Subgroup analysis based on previous treatment with other disease-modifying agents showed significant subgroup difference favoring those who were treated before (P-value = 0.0982). However, subgrouping according to dose (standard versus high) did not show significant subgroup difference (P-value = 0.2439). The pooled percentage of event-free survival was 78% [95% CI: 66:87]. Subgroup analysis based on previous treatment with other disease-modifying therapies did not demonstrate significant subgroup difference (P-value = 0.3313). However, subgrouping according to dose exhibited significant subgroup difference favoring high dose (P-value = 0.0005). Overall, serious, and drug-related adverse effects showed pooled proportion of 94% [95% CI: 75:100], 30% [95% CI: 9:57], and 63% [95% CI: 49:75], respectively. Thrombocytopenia was the most frequent adverse event. For the change from baseline in CHOP-Intend score, the pooled effect estimate was 15.77 [95% CI:12.07:19.47], and subgrouping according to previous treatment with disease-modifying agents showed significant subgroup difference (P-value = 0.0817). Conclusion: Onasemnogene improves chances of survival in SMA1 patients, especially if patients had previous treatment, significantly improves motor abilities, and is generally tolerable.