文摘
摘要目的:提出中期业绩的持续培养研究(NCT02386553)的疗效和安全性研究鞘内nusinersen婴儿发生前症状在2或3SMN2副本。
背景:Nusinersen是第一个批准治疗SMA。
设计/方法:登记婴儿起初≤6周剂量,发生前症状临床和基因诊断为SMA。主要终点是死亡时间或呼吸系统干预(≥6小时/天连续≥7天或气管造口术)。
结果:培养了25婴儿(2份SMN2,n = 15;3册,n = 10)。截至2019年3月29日,最后一次访问时的平均年龄为34.8岁(范围25.7 - -45.4)个月。所有婴儿还活着,没有一个需要永久通风。中位数时间死亡或呼吸道干预无法估计,因为太少的事件。四个婴儿(所有2SMN2张)需要呼吸干预≥6小时/天连续≥7天,在急性情况下启动,可逆疾病。所有25个婴儿获得世卫组织运动里程碑坐在没有支持和23/25(92%)与援助实现行走;22/25(88%)的独自走。大多数孩子实现这些动作的里程碑(21/25[84%]坐在没有支持,15/23(65%)和援助,和16/22(73%)独立行走)在99年th百分位建立的窗口岁健康儿童。几乎所有孩子达到的最高分数排计划的规模。磷酸化神经丝重链(pNF-H)水平迅速下降在加载阶段nusinersen然后稳定下来。等离子体pNF-H水平64天与电动机里程碑独自年龄显著相关(r年代= 0.64;p = 0.0025;n = 20)。将额外pNF-H相关性分析。没有确定新的安全问题。
结论:这些数据表明了继续受益婴儿发起nusinersen在症状出现之前,强调新生儿筛查和早期治疗的价值。
研究支持:生原体
披露:芬克尔博士已经收到个人赔偿咨询、担任科学顾问委员会说,或其他活动的顾问费用和Ionis制药,inc .的喜爱和珍惜;顾问AveXis、诺华和罗氏公司;数据安全监测委员会AveXis avx - 101第1阶段基因转移研究和罗氏翻车鱼阶段1 b;咨询capacit。芬克尔博士已经收到赔偿服务特许使用金的董事会从费城儿童医院的许可费获得使用切意愿运动机能。芬克尔博士已经收到版税、许可费或合同权利支付从费城儿童医院的特许使用金的获得使用许可费用砍意愿运动机能。芬克尔博士已经收到资助研究支持和Ionis制药,期间公司的喜爱和珍惜;从AveXis赠款,Cytokinetics,罗氏。博士德体内已收到个人赔偿咨询、担任科学顾问委员会说,与顾问/顾问AveXis或其他活动,生原体,Cytokinetics, Ionis制药、Metafora,罗氏公司,赛诺菲-安万特(sanofi - aventis) Santhera, Sarepta,学者岩石,PTC, Ultragenyx,治愈SMA和SMA基金会。博士德体内已经收到资助研究支持从生原体/临床试验支持,CureSMA,希望孩子研究基金会,Mallinckrodt,美国国立卫生研究院,PTC, Santhera, Sarepta,学者岩石,SMA基金会Ultragenyx,研究所,Glut1缺乏基础,和美国Swoboda博士已经收到个人赔偿咨询、担任科学顾问委员会说,与顾问委员会或其他活动AveXis和生原体。 Dr. Swoboda has received research support from Clinical trial funding from Biogen and Ionis Pharmaceuticals Inc. for the CS1, CS2, CS12 and NURTURE studies. Dr. Bertini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor/consultant for AveXis, Biogen, Edison, Novartis and Roche. Dr. Bertini has received research support from Grants from Fondazione Telethon and the Italian Ministry of Health. Dr. Wuh-Liang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor/consultant for Biogen. Dr. Wuh-Liang has received research support from Grants from Biogen. Dr. Foster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Biogen. Dr. Foster holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Bhan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Bhan holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Fradette has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employees of and hold stock/stock options in Ionis. Dr. Fradette has received compensation for serving on the Board of Directors of Biogen, compensation includes stock. Dr. Fradette holds stock and/or stock options in Biogen, stock greater than 10K which sponsored research in which Dr. Fradette was involved as an investigator. Dr. Farwell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Farwell holds stock and/or stock options in Biogen.
