Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA).
Motor function
Risdiplam
SMA
SUNFISH
Safety
Spinal muscular atrophy
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
26
10
2022
accepted:
08
01
2023
revised:
06
01
2023
medline:
27
4
2023
pubmed:
4
2
2023
entrez:
3
2
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36735057
doi: 10.1007/s00415-023-11560-1
pii: 10.1007/s00415-023-11560-1
pmc: PMC9897618
doi:
Substances chimiques
Risdiplam
76RS4S2ET1
Pyrimidines
0
Azo Compounds
0
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2531-2546Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
Références
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