Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy : Findings from the RESTORE Registry
Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials.
Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.
Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources.
Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related.
Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Journal of neuromuscular diseases - 11(2024), 2 vom: 04., Seite 425-442 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Servais, Laurent [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 30.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.3233/JND-230122 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367412845 |
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| 100 | 1 | |a Servais, Laurent |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy |b Findings from the RESTORE Registry |
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| 500 | |a Date Completed 12.03.2024 | ||
| 500 | |a Date Revised 30.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials | ||
| 520 | |a Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting | ||
| 520 | |a Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources | ||
| 520 | |a Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related | ||
| 520 | |a Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AAV9 vector-based gene replacement therapy | |
| 650 | 4 | |a RESTORE registry | |
| 650 | 4 | |a long-term follow-up | |
| 650 | 4 | |a motor neuron disease | |
| 650 | 4 | |a newborn screening | |
| 650 | 4 | |a onasemnogene abeparvovec | |
| 650 | 4 | |a outcomes | |
| 650 | 4 | |a rare disease | |
| 650 | 4 | |a real-world evidence | |
| 650 | 4 | |a spinal muscular atrophy | |
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| 650 | 7 | |a Recombinant Fusion Proteins |2 NLM | |
| 700 | 1 | |a Day, John W |e verfasserin |4 aut | |
| 700 | 1 | |a De Vivo, Darryl C |e verfasserin |4 aut | |
| 700 | 1 | |a Kirschner, Janbernd |e verfasserin |4 aut | |
| 700 | 1 | |a Mercuri, Eugenio |e verfasserin |4 aut | |
| 700 | 1 | |a Muntoni, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Proud, Crystal M |e verfasserin |4 aut | |
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| 700 | 1 | |a Tizzano, Eduardo F |e verfasserin |4 aut | |
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| 700 | 1 | |a Anderson, Frederick A |e verfasserin |4 aut | |
| 700 | 1 | |a Finkel, Richard S |e verfasserin |4 aut | |
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