Departments of Pediatrics and Neurology and Neurosurgery, McGill University, Montreal, Canada.
Department of Neurology, Stanford University, Palo Alto, CA, USA.
J Neurol. 2023 May;270(5):2531-2546. doi: 10.1007/s00415-023-11560-1. Epub 2023 Feb 3.
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.
利司扑兰是一种口服运动神经元 2（SMN2）前体 mRNA 剪接修饰剂，用于治疗脊髓性肌萎缩症（SMA）。SUNFISH（NCT02908685）第 2 部分是一项 3 期、随机、双盲、安慰剂对照研究，旨在评估利司扑兰治疗 2 型和非卧床 3 型 SMA 的疗效和安全性。主要终点达到：与安慰剂相比，利司扑兰治疗 12 个月后，32 项运动功能测量（MFM32）总分的基线变化显著更大。12 个月后，所有参与者均接受利司扑兰治疗，同时保留初始治疗的盲法。我们在此人群中报告了 24 个月的疗效和安全性结果。24 个月的探索性终点包括 MFM32 的基线变化和安全性。MFM 衍生的结果与外部对照进行比较。利司扑兰治疗 24 个月时，32%的患者 MFM32 总分较基线改善（≥3）；58%的患者病情稳定（≥0）。与外部对照相比，MFM 衍生评分中观察到利司扑兰的治疗差异为 3.12（95%置信区间 [CI] 1.67-4.57）。总体而言，12 个月时运动功能的改善在 24 个月时得以维持或进一步改善。在最初接受安慰剂的患者中，与基线相比，12 个月的利司扑兰治疗后 MFM32 保持稳定（0.31 [95%CI -0.65 至 1.28]）；16%的患者评分改善，59%的患者病情稳定。24 个月时的安全性与 12 个月时观察到的安全性一致。利司扑兰治疗 24 个月后，运动功能进一步改善或稳定，证实了长期治疗的益处。
