Dep Genetics UFRGS, Casa dos Raros, INAGEMP, Med Genet Serv HCPA, and DASA Genomics, Porto Alegre, Brazil.
Hospital Universitario Virgen del Rocio, Seville, Spain.
Orphanet J Rare Dis. 2024 May 7;19(1):189. doi: 10.1186/s13023-024-03176-z.
Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.
This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.
As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and - 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.
To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.
黏多糖贮积症 VII 型（MPS VII）是一种罕见的常染色体隐性、进行性、衰弱性溶酶体贮积病，由β-葡糖醛酸酶（GUS）活性降低引起。静脉注射酶替代疗法维斯替诺酶阿尔法（重组人 GUS）是一种已批准用于 MPS VII 患者的治疗方法。
本疾病监测计划（DMP）是一项正在进行的、多中心观察性研究，从接受维斯替诺酶阿尔法治疗或任何其他管理方法的 MPS VII 患者（计划纳入约 50 名患者）中收集标准化的真实世界数据。数据按照良好临床实践指南进行监测和记录，并每年对捕获的数据进行计划的中期分析。截至 2022 年 11 月 17 日，我们在此总结安全性和疗效结果。
截至数据截止日期，已有 35 名患者入组：28 名在治疗组，7 名在未治疗组。MPS VII 诊断时的平均（SD）年龄为 4.5（4.0）岁（范围，0.0 至 12.4 岁），DMP 入组时的平均（SD）年龄为 13.9（11.1）岁（范围，1.5 至 50.2 岁）。10 名患者（29%）有非免疫性胎儿水肿史。在 23 名在 DMP 入组前开始治疗的患者中，三种尿糖胺聚糖（uGAG）的初始基线至 DMP 入组的平均排泄量发生了显著变化：硫酸皮肤素（DS），-84%；硫酸软骨素（CS），-55%；硫酸乙酰肝素（HS），-42%。在该组中，从初始基线到第 6、12 和 24 个月的平均降幅也保持不变：uGAG DS（-84%、-87%、-89%）、CS（-70%、-71%、-76%）和 HS（+3%、-32%和-41%）。所有不良事件（AE）均与已知的维斯替诺酶阿尔法安全性特征一致。没有患者停止使用维斯替诺酶阿尔法。一名患者死亡。
迄今为止，DMP 已收集了宝贵的 MPS VII 疾病特征数据。维斯替诺酶阿尔法的获益风险状况保持不变，对治疗儿科和成年 MPS VII 患者仍然有利。DS 和 CS uGAG 的减少表明维斯替诺酶阿尔法在第 24 个月时仍有效。目前正在招募患者。
