Therapeutic Efficacy and Safety of Onasemnogene Abeparvovec Gene Therapy for Spinal Muscular Atrophy Type 1: Updated Systematic Review with Meta-analysis
George Hanen1, Sarah Alfaqaih2, Hazem Mohammed3, Mohamed Nasser1, Mohamed Haseeb1, Hatem Yaser3, Shehab Yaser3, Mohamed Darwish1, Mostafa Meshref4
1Minia University, School of Medicine, Minia, Egypt, 2Department of Pediatrics, Faculty of Medicine, Misurata, Libya, 3Faculty of Medicine, Assiut University, Assiut, Egypt, 4Department of Neurology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
Objective:
Our objective is to evaluate the efficacy and safety of onasemnogene abeparvovec in spinal muscular atrophy type 1 (SMA1) patients.
Background:
Onasemnogene is a gene therapy approved by the U.S. Food and Drug Administration in May 2019. It offers the unique benefit of single-time dose administration. The therapy has since been approved for the treatment of SMA1 patients in multiple countries.
Design/Methods:
A 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 on safety and efficacy outcomes. Safety outcomes include 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 risk ratios (RR) for dichotomous data and mean change from baseline for continuous data with 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). The pooled percentage of event-free survival was 78% [95% CI: 66:87]. Subgrouping according to dose (standard vs high) exhibited significant subgroup difference favoring high dose (P-value = 0.0005). Overall, serious and drug-related adverse effects showed pooled proportions 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).
Conclusions:
Onasemnogene improves chances of survival in SMA1 patients, especially if patients had previous treatment, significantly improves motor abilities, and is generally tolerable.
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