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Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)

Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and...

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Autores principales: Oskoui, Maryam, Day, John W., Deconinck, Nicolas, Mazzone, Elena S., Nascimento, Andres, Saito, Kayoko, Vuillerot, Carole, Baranello, Giovanni, Goemans, Nathalie, Kirschner, Janbernd, Kostera-Pruszczyk, Anna, Servais, Laurent, Papp, Gergely, Gorni, Ksenija, Kletzl, Heidemarie, Martin, Carmen, McIver, Tammy, Scalco, Renata S., Staunton, Hannah, Yeung, Wai Yin, Fontoura, Paulo, Mercuri, Eugenio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897618/
https://www.ncbi.nlm.nih.gov/pubmed/36735057
http://dx.doi.org/10.1007/s00415-023-11560-1
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author Oskoui, Maryam
Day, John W.
Deconinck, Nicolas
Mazzone, Elena S.
Nascimento, Andres
Saito, Kayoko
Vuillerot, Carole
Baranello, Giovanni
Goemans, Nathalie
Kirschner, Janbernd
Kostera-Pruszczyk, Anna
Servais, Laurent
Papp, Gergely
Gorni, Ksenija
Kletzl, Heidemarie
Martin, Carmen
McIver, Tammy
Scalco, Renata S.
Staunton, Hannah
Yeung, Wai Yin
Fontoura, Paulo
Mercuri, Eugenio
author_facet Oskoui, Maryam
Day, John W.
Deconinck, Nicolas
Mazzone, Elena S.
Nascimento, Andres
Saito, Kayoko
Vuillerot, Carole
Baranello, Giovanni
Goemans, Nathalie
Kirschner, Janbernd
Kostera-Pruszczyk, Anna
Servais, Laurent
Papp, Gergely
Gorni, Ksenija
Kletzl, Heidemarie
Martin, Carmen
McIver, Tammy
Scalco, Renata S.
Staunton, Hannah
Yeung, Wai Yin
Fontoura, Paulo
Mercuri, Eugenio
author_sort Oskoui, Maryam
collection PubMed
description Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67–4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI – 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-023-11560-1.
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spelling pubmed-98976182023-02-06 Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA) Oskoui, Maryam Day, John W. Deconinck, Nicolas Mazzone, Elena S. Nascimento, Andres Saito, Kayoko Vuillerot, Carole Baranello, Giovanni Goemans, Nathalie Kirschner, Janbernd Kostera-Pruszczyk, Anna Servais, Laurent Papp, Gergely Gorni, Ksenija Kletzl, Heidemarie Martin, Carmen McIver, Tammy Scalco, Renata S. Staunton, Hannah Yeung, Wai Yin Fontoura, Paulo Mercuri, Eugenio J Neurol Original Communication Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67–4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI – 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-023-11560-1. Springer Berlin Heidelberg 2023-02-03 2023 /pmc/articles/PMC9897618/ /pubmed/36735057 http://dx.doi.org/10.1007/s00415-023-11560-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Communication
Oskoui, Maryam
Day, John W.
Deconinck, Nicolas
Mazzone, Elena S.
Nascimento, Andres
Saito, Kayoko
Vuillerot, Carole
Baranello, Giovanni
Goemans, Nathalie
Kirschner, Janbernd
Kostera-Pruszczyk, Anna
Servais, Laurent
Papp, Gergely
Gorni, Ksenija
Kletzl, Heidemarie
Martin, Carmen
McIver, Tammy
Scalco, Renata S.
Staunton, Hannah
Yeung, Wai Yin
Fontoura, Paulo
Mercuri, Eugenio
Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)
title Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)
title_full Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)
title_fullStr Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)
title_full_unstemmed Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)
title_short Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA)
title_sort two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (sma)
topic Original Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897618/
https://www.ncbi.nlm.nih.gov/pubmed/36735057
http://dx.doi.org/10.1007/s00415-023-11560-1
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