Anjum Ahmad Furqan, Anjum Muhammad Burhan, Rehman Raza Ur
Shaikh Khalifa Bin Zayed Al-Nahyan Medical College, Shaikh Zayed Postgraduate Medical Institute (SZPGMI), Lahore, Pakistan.
Akhtar Saeed Medical and Dental College, Lahore, Pakistan.
Curr Ther Res Clin Exp. 2025 Mar 25;102:100787. doi: 10.1016/j.curtheres.2025.100787. eCollection 2025.
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder with limited treatment options beyond corticosteroids, which have significant adverse effects. Givinostat, a histone deacetylase inhibitor, has recently emerged as a promising disease-modifying therapy. This commentary examines the therapeutic potential of givinostat, its mechanism of action, and the clinical evidence supporting its role in DMD treatment.
A review of the EPIDYS Phase 3 trial and supporting clinical studies was conducted. The study included boys aged 6 to 17 years with genetically confirmed DMD, assessing givinostat's efficacy and safety over 18 months. Key endpoints included the North Star Ambulatory Assessment (NSAA), MRI-based muscle preservation, and adverse event (AE) profiles.
Givinostat-treated patients demonstrated a 1.9-point higher NSAA score compared to placebo ( = 0.03), with significant reductions in muscle fat infiltration (40% lower than placebo; < 0.05). Functional tests showed trends toward improved stair-climbing ability, though not statistically significant. AEs included thrombocytopenia (20%) and hypertriglyceridemia (10%), necessitating monitoring but remaining manageable.
Givinostat represents a paradigm shift in DMD management, offering benefits beyond corticosteroids by reducing fibrosis and promoting muscle regeneration. While its long-term safety and cost-effectiveness require further evaluation, its combination potential with gene therapies highlights its importance in future DMD treatment strategies. Ongoing studies aim to refine its role in broader neuromuscular disorders.
杜氏肌营养不良症（DMD）是一种进行性神经肌肉疾病，除了具有显著副作用的皮质类固醇外，治疗选择有限。吉维司他，一种组蛋白脱乙酰酶抑制剂，最近已成为一种有前景的疾病修饰疗法。本评论探讨了吉维司他的治疗潜力、作用机制以及支持其在DMD治疗中作用的临床证据。
对EPIDYS 3期试验及相关临床研究进行了综述。该研究纳入了6至17岁经基因确诊为DMD的男孩，评估了吉维司他在18个月内的疗效和安全性。主要终点包括北极星动态评估（NSAA）、基于MRI的肌肉保存情况以及不良事件（AE）概况。
与安慰剂相比，接受吉维司他治疗的患者NSAA评分高1.9分（=0.03），肌肉脂肪浸润显著减少（比安慰剂低40%；<0.05）。功能测试显示爬楼梯能力有改善趋势，但无统计学意义。不良事件包括血小板减少症（20%）和高甘油三酯血症（10%），需要监测但仍可控制。
吉维司他代表了DMD治疗模式的转变，通过减少纤维化和促进肌肉再生，提供了超越皮质类固醇的益处。虽然其长期安全性和成本效益需要进一步评估，但其与基因疗法的联合潜力凸显了其在未来DMD治疗策略中的重要性。正在进行的研究旨在明确其在更广泛的神经肌肉疾病中的作用。
