Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Nathalie Guffon, Line Borgwardt, Anna Tylki-Szymańska, Andrea Ballabeni, Francesca Donà, Amer Joseph, Henriët Nienhuis, Caterina Maugeri, Allan Lund
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引用次数: 0

Abstract

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

α-甘露糖苷酶病患者接受 velmanase alfa 治疗长达 12 年的长期疗效和安全性。
使用velmanase alfa的酶替代疗法(ERT)曾在α-甘露糖苷酶病患者长达4年的治疗中显示出良好的疗效和安全性。这项汇总分析来自两项多中心、开放标签的IIIb期扩展试验rhLAMAN-07(N = 13;NCT01908712)和rhLAMAN-09(N = 8;NCT01908725),评估了velmanase alfa的长期疗效。16名曾完成rhLAMAN-02/-03/-04/-05/-08 I-III期试验的患者和5名对ERT无效的患者被纳入研究。患者每周接受一次1 mg/kg velmanase alfa治疗。终点包括血清寡糖、6分钟步行测试(6MWT)、3分钟爬楼梯测试(3MSCT)、肺功能(用力肺活量[FVC],预测值%)、血清免疫球蛋白G(IgG)水平和不良事件与治疗基线(在任何试验中首次服用 velmanase alfa 之前)相比的变化。整个队列由 21 名患者组成,按治疗基线时的年龄分为儿童亚组(14 人)和成人亚组(7 人)。儿科患者的 6MWT 步行距离增加或保持稳定,而成人患者则保持稳定或略有下降。同样,儿科患者在 3MSCT 中的表现更好。在大约 6 年的观察期内,两个亚组的预测肺活量(FVC)变化不相上下,之后则出现了差异。总体而言,在开始治疗时就能观察到血清寡糖清除率和血清 IgG 水平持续上升,并一直持续到最后一次共同观察。Velmanase alfa 治疗的耐受性总体良好,报告的不良反应大多为轻度至中度。在长达12年的随访中,长期疗效和安全性结果表明,velmanase alfa对α-甘露糖苷酸病患者仍有益处。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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