Vestronidase alfa (recombinant human beta-glucuronidase) is an enzyme replacement therapy (ERT) for Mucopolysaccharidosis (MPS) VII, a highly heterogeneous, ultra-rare disease. Twelve subjects, ages 8-25 years, completed a Phase 3, randomized, placebo-controlled, blind-start, single crossover study (UX003-CL301; NCT02377921), receiving 24-48 weeks of vestronidase alfa 4 mg/kg IV. All 12 subjects completed the blind-start study, which showed significantly reduced urinary glycosaminoglycans (GAG) and clinical improvement in a multi-domain responder index, and enrolled in a long-term, open-label, extension study (UX003-CL202; NCT02432144). Here, we report the final results of the extension study, up to an additional 144 weeks after completion of the blind-start study. Three subjects (25%) completed all 144 weeks of study, eight subjects (67%) ended study participation before Week 144 to switch to commercially available vestronidase alfa, and one subject discontinued due to non-compliance after receiving one infusion of vestronidase alfa in the extension study. The safety profile of vestronidase alfa in the extension study was consistent with observations in the preceding blind-start study, with most adverse events mild to moderate in severity. There were no treatment or study discontinuations due to AEs and no noteworthy changes in a standard safety chemistry panel. Out of the eleven subjects who tested positive for anti-drug antibodies at any time during the blind-start or extension study, including the baseline assessment in the blind-start study, seven subjects tested positive for neutralizing antibodies and all seven continued to demonstrate a reduction in urinary GAG levels. There was no association between antibody formation and infusion associated reactions. Subjects receiving continuous vestronidase alfa treatment showed a sustained urinary GAG reduction and clinical response evaluated using a multi-domain responder index that includes assessments in pulmonary function, motor function, range of motion, mobility, and visual acuity. Reduction in fatigue was also maintained in the overall population. As ERT is not expected to cross the blood brain barrier, limiting the impact on neurological signs of disease, and not all subjects presented with neurological symptoms, outcomes related to central nervous system pathology are not focused on in this report. Results from this study show the long-term safety and durability of clinical efficacy in subjects with MPS VII with long-term vestronidase alfa treatment.

中文翻译：

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乙醛酸脱氢酶α，rhGUS酶替代疗法在粘多糖贮积症患者中的长期安全性和有效性。

Vestronidase alfa（重组人β-葡糖醛酸糖苷酶）是一种用于治疗粘多糖贮积病（MPS）VII（一种高度异质，极少见的疾病）的酶替代疗法（ERT）。12名年龄在8-25岁之间的受试者完成了一项3期随机，安慰剂对照，盲法，单次交叉研究（UX003-CL301； NCT02377921），接受了24-48周的4 mg / kg阿尔法酮酶治疗。所有12名受试者均完成了盲目的研究，该研究显示尿糖胺聚糖（GAG）显着降低，并且多域反应者指数的临床改善，并参加了一项长期的开放标签扩展研究（UX003-CL202; NCT02432144 ）。在这里，我们报告了扩展研究的最终结果，直到完成盲目的研究后又延长了144周。三位受试者（25％）完成了所有144周的学习，八名受试者（67％）在第144周前结束了研究参加，转而使用市售的阿尔法糖苷酶α，并且一名受试者因在扩展研究中接受一剂乙炔酶的输注后因不依从而中断。延伸研究中的阿维诺酮酶α的安全性与先前的盲法研究中的观察结果一致，大多数不良事件的严重程度为轻度至中度。没有因不良事件引起的治疗或研究中断，并且标准安全化学小组中没有值得注意的变化。在盲法开始或扩展研究期间任何时间（包括盲法开始研究的基线评估）中抗药物抗体测试均为阳性的11名受试者中，7名受试者的中和抗体测试阳性，所有7名受试者继续证明尿GAG水平降低。抗体形成与输注相关反应之间没有关联。接受持续的阿尔法酮酶治疗的受试者表现出持续的尿GAG降低，并使用多域反应指数评估临床反应，该指数包括肺功能，运动功能，运动范围，活动性和视力的评估。总体人群也保持了疲劳的减轻。由于不能期望ERT跨越血脑屏障，从而限制了对疾病神经系统症状的影响，并且并非所有出现神经系统症状的受试者，因此本报告并未重点关注与中枢神经系统病理相关的结果。