Onasemnogene abparvovec基因替代治疗后1型脊髓性肌萎缩的早期干预和快速见效：汇总临床研究数据的事后分析结果

IF 4.8 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-10-01 Epub Date: 2025-07-07 DOI:10.1007/s40120-025-00791-1

Walter Toro, Sandra P Reyna, Shannon Ritter, Anish Patel, Nayla Mumneh, Omar Dabbous

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引用次数: 0

摘要

研究表明，对脊髓性肌萎缩症（SMA）进行疾病改善治疗的早期干预可能为获得最佳结果提供了最佳机会。其中一种治疗方法是onasemnogene abparvovec，这是一种基因替代疗法，在临床试验、长期研究和实际数据（例如RESTORE登记）中证明了持久的疗效。方法：通过事后分析，评估静脉注射onasemnogene abparvovec对有症状的1型SMA婴儿（即非静坐者）的运动功能和无事件生存的早期影响。对参加START、STR1VE-US和STR1VE-EU临床试验的患者进行费城儿童医院婴儿神经肌肉疾病测试（CHOP意图）评分和无事件生存评估。结果：共纳入67例患者。CHOP intention基线平均（SD）评分为29.3（9.58）分。在给药后1个月、2个月和3个月，平均CHOP intention分别快速增加7.0、9.7和11.8点。在给药后6个月，54/59例（91.5%）接受onasemnogene abparvovec治疗的婴儿CHOP intention评分较基线改善≥4分，平均（SD） CHOP intention评分为44.3（9.92）分。与自然史患者相比，接受onasemnogene abparvovec治疗的患者无通气生存期更长，在整个随访过程中，与自然史队列的分离具有统计学意义。结论：onasemnogene abparvovec治疗的症状性1型SMA患者的运动功能得到了快速且具有临床意义的改善。早期诊断和治疗对于及时恢复和保存运动神经元和最大限度地改善运动功能至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Early Intervention and Speed-to-Effect in Spinal Muscular Atrophy Type 1 Following Onasemnogene Abeparvovec Gene Replacement Therapy: Results of aPost-Hoc Analysis of Pooled Clinical Study Data.

查看原文本刊更多论文

Early Intervention and Speed-to-Effect in Spinal Muscular Atrophy Type 1 Following Onasemnogene Abeparvovec Gene Replacement Therapy: Results of aPost-Hoc Analysis of Pooled Clinical Study Data.

Introduction: Studies suggest that early intervention with disease-modifying treatment for spinal muscular atrophy (SMA) might provide the best opportunity for optimal outcomes. One such treatment is onasemnogene abeparvovec, a gene replacement therapy with durable efficacy demonstrated in clinical trials, long-term studies, and real-world data (e.g., RESTORE registry).

Methods: A pooled post-hoc analysis was conducted to assess the early post-treatment impact of intravenous onasemnogene abeparvovec on motor function and event-free survival for symptomatic infants with SMA type 1 (i.e., non-sitters). Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores and event-free survival were evaluated for patients enrolled in the START, STR1VE-US, and STR1VE-EU clinical trials.

Results: The pooled analysis set included 67 patients. Mean (SD) CHOP INTEND score at baseline was 29.3 (9.58) points. Rapid increases in mean CHOP INTEND of 7.0, 9.7, and 11.8 points were observed at 1, 2, and 3 months post-dose, respectively. At 6 months post-dose, 54/59 infants (91.5%) treated with onasemnogene abeparvovec achieved a clinically significant ≥ 4-point improvement in CHOP INTEND score from baseline, with a mean (SD) CHOP INTEND score of 44.3 (9.92) points. Patients who received onasemnogene abeparvovec had longer ventilation-free survival compared with natural history, with a statistically significant separation from the natural history cohort being maintained throughout follow-up.

Conclusions: Rapid and clinically significant improvements in motor function were observed for onasemnogene abeparvovec-treated patients with symptomatic SMA type 1. Early diagnosis and treatment are essential for timely restoration and preservation of motor neurons and maximal motor function improvement.

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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