Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial.
Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial.
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Onasemnogene abeparvovec治疗有2个SMN2拷贝的1型脊髓性肌萎缩症风险的前驱婴儿：III期SPR1NT试验
DOI：
10.1038/s41591-022-01866-4
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发表时间：
2022-07
期刊：
影响因子：
82.9
通讯作者：
Macek, Thomas A.
中科院分区：
文献类型：
--
作者：
Strauss, Kevin A.;Farrar, Michelle A.;Muntoni, Francesco;Saito, Kayoko;Mendell, Jerry R.;Servais, Laurent;McMillan, Hugh J.;Finkel, Richard S.;Swoboda, Kathryn J.;Kwon, Jennifer M.;Zaidman, Craig M.;Chiriboga, Claudia A.;Iannaccone, Susan T.;Krueger, Jena M.;Parsons, Julie A.;Shieh, Perry B.;Kavanagh, Sarah;Tauscher-Wisniewski, Sitra;McGill, Bryan E.;Macek, Thomas A.
SPR1NT(NCT03505099)是一项第三阶段、多中心、单臂研究，旨在调查在≤治疗6周大的双等位基因突变的症状前儿童的疗效和安全性。在这里，我们报告了14名儿童的最终结果，这些儿童有两个SMN2拷贝，预计会发展为1型脊肌萎缩症。疗效与匹配的儿科神经肌肉临床研究自然病史队列(n = 23)进行了比较。所有14名登记的婴儿在任何18个月的探视中都独立坐着≥30 秒(贝利-III项目26；P≤<； ； 0.001；11在正常发育窗口内)。根据方案，所有患者在14个月没有永久机械通气的情况下存活；13人在18个月期间保持体重(≥第三个百分位数)。没有儿童使用营养或呼吸支持。研究人员未考虑与治疗有关的严重不良事件。Onasemnogene abepparvovec对有望发展为SMA 1型的儿童有效且耐受性良好，突显了普遍进行新生儿筛查的紧迫性。对于有SMA 1型风险的症状前婴儿，与未经治疗或经治疗的有症状的患者相比，onasemnogene abparvovec可改善运动结果、无呼吸机生存和营养/呼吸独立性。
SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26; P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening. For presymptomatic infants at risk for SMA type 1, onasemnogene abeparvovec improves motor outcomes, ventilator-free survival, and nutritional/respiratory independence compared with untreated or treated symptomatic patients
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影响因子：
15.1
作者：
Kariyawasam DST;D'Silva AM;Vetsch J;Wakefield CE;Wiley V;Farrar MA
通讯作者：
Farrar MA
影响因子：
4.2
作者：
Day JW;Mendell JR;Mercuri E;Finkel RS;Strauss KA;Kleyn A;Tauscher-Wisniewski S;Tukov FF;Reyna SP;Chand DH
通讯作者：
Chand DH
影响因子：
4.6
作者：
Boemer F;Caberg JH;Beckers P;Dideberg V;di Fiore S;Bours V;Marie S;Dewulf J;Marcelis L;Deconinck N;Daron A;Blasco-Perez L;Tizzano E;Hiligsmann M;Lombet J;Pereira T;Lopez-Granados L;Shalchian-Tehran S;van Assche V;Willems A;Huybrechts S;Mast B;van Olden R;Dangouloff T;Servais L
通讯作者：
Servais L
影响因子：
2.8
作者：
Dangouloff, Tamara;Burghes, Arthur;Servais, Laurent
通讯作者：
Servais, Laurent
影响因子：
9.9
作者：
Finkel, Richard S.;McDermott, Michael P.;De Vivo, Darryl C.
通讯作者：
De Vivo, Darryl C.