Drug updated on 4/18/2024
| Dosage Form | Infusion (intravenous: 5.5 mL, 8.3 mL) |
| Drug Class | Adeno-associated virus vector-based gene therapies |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Summary
- Onasemnogene abeparvovec-xioi (Zolgensma) is indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA), demonstrating significant improvements in motor function and achievements in motor milestones, with notable observations in presymptomatic or early-treated individuals.
- Six systematic reviews and meta-analyses were examined to gather information about Zolgensma. These studies reveal various aspects regarding its efficacy and safety, specifically in comparison to other available treatments such as Nusinersen and Risdiplam.
- Indirect comparisons suggest that while Risdiplam may offer better survival and motor function over Nusinersen for Type 1 SMA, direct comparisons with Zolgensma are difficult due to differences in study populations. However, when indirectly compared to Nusinersen, Zolgensma suggests longer event-free survival and a higher likelihood of achieving independent sitting milestones.
- Common side effects associated with Zolgensma include fever, vomiting, low platelet count, and elevated liver enzymes; these adverse events were more common in patients older than 8 months. The safety profile appears distinct from those reported for Nusinersen and Risdiplam, considering it is a one-time gene therapy treatment requiring different management strategies.
- Initiating treatment early significantly affects outcomes towards an almost normal development trajectory, emphasizing the importance of early detection. Most evidence focuses on SMA Type 1, but there is some insight into applicability to Types 2 - 4, although data is limited, warranting further investigation into its effectiveness within these groups.
- Despite being a groundbreaking advancement offering potential improvements previously unattainable, especially for SMA Type 1 patients due to its convenience as a one-time administration, therapy choice should be carefully considered, taking into account the individual patient’s condition, including their age, type of SMA, potential benefits, and risks associated with each treatment option, necessitating further comparisons and real-world efficacy and safety data.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Zolgensma (onasemnogene abeparvovec-xioi) Prescribing Information. | 2023 | Novartis Gene Therapies, Inc., Bannockburn, IL |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy. | 2021 | Muscle & Nerve |
| From clinical trials to clinical practice: practical considerations for gene replacement therapy in sma type 1. | 2019 | Pediatric Neurology |