Crawford Thomas O, Day John W, De Vivo Darryl C, Krueger Jena M, Mercuri Eugenio, Nascimento Andres, Pasternak Amy, Mazzone Elena Stacy, Duong Tina, Song Guochen, Marantz Jing L, Baver Scott, Yu Dongzi, Liu Lan, Darras Basil T
Johns Hopkins Medical, Baltimore, MD, United States.
Stanford Neuroscience Health Center, Palo Alto, CA, United States.
Front Neurol. 2024 Jul 22;15:1419791. doi: 10.3389/fneur.2024.1419791. eCollection 2024.
At 12 months in the phase 2 TOPAZ study, treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable safety profile. This manuscript reports the extended efficacy and safety in the nonambulatory group of the TOPAZ study at 36 months.
Patients who completed the primary study (NCT03921528) could enroll in an open-label extension, during which patients received apitegromab 20 mg/kg by intravenous infusion every 4 weeks. Patients were assessed periodically via the Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), World Health Organization (WHO) motor development milestones, Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) Daily Activities and Mobility domains, and Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire.
Of the 58 patients enrolled in TOPAZ, 35 were nonambulatory (mean age 7.3 years). The mean change at 36 months in HFMSE score from baseline was +4.0 (standard deviation [SD]: 7.54), and + 2.4 (3.24) for RULM score (excluding = 7 after scoliosis surgery). Caregiver-reported outcomes (PEDI-CAT and PROMIS Fatigue) showed improvements from baseline over 36 months. In addition, most patients (28/32) improved or maintained WHO motor milestones achieved at baseline. The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%).
The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings.
在2期TOPAZ研究的12个月时，阿皮特格罗单抗治疗与2型或3型脊髓性肌萎缩（SMA）患者运动功能改善及良好的安全性相关。本手稿报告了TOPAZ研究非行走组36个月时的扩展疗效和安全性。
完成初步研究（NCT03921528）的患者可参加开放标签扩展研究，在此期间患者每4周接受一次20mg/kg阿皮特格罗单抗静脉输注。通过哈默史密斯功能运动量表扩展版（HFMSE）、修订上肢模块（RULM）、世界卫生组织（WHO）运动发育里程碑、残疾儿童评定量表计算机自适应测试（PEDI-CAT）日常活动和移动领域以及患者报告结局测量信息系统（PROMIS）疲劳问卷对患者进行定期评估。
在TOPAZ研究入组的58例患者中，35例为非行走患者（平均年龄7.3岁）。HFMSE评分在36个月时相对于基线的平均变化为+4.0（标准差[SD]：7.54），RULM评分为+2.4（3.24）（脊柱侧弯手术后除外=7）。照料者报告的结局（PEDI-CAT和PROMIS疲劳）显示在36个月内较基线有所改善。此外，大多数患者（28/32）改善或维持了基线时达到的WHO运动里程碑。最常报告的治疗中出现的不良事件为发热（48.6%）、鼻咽炎（45.7%）、COVID-19感染（40.0%）、呕吐（40.0%）和上呼吸道感染（31.4%）。
在12个月时观察到的阿皮特格罗单抗治疗益处持续至36个月，且无新的安全性发现。
