A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Myrl Holida, Aleš Linhart, Antonio Pisani, Nicola Longo, François Eyskens, Ozlem Goker-Alpan, Eric Wallace, Patrick Deegan, Camilla Tøndel, Ulla Feldt-Rasmussen, Derralynn Hughes, Anat Sakov, Rossana Rocco, Einat Brill Almon, Sari Alon, Raul Chertkoff, David G Warnock, Stephen Waldek, William R Wilcox, John A Bernat
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引用次数: 0

Abstract

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

这是一项 III 期开放标签临床试验,评估每 4 周给法布里病成人患者服用 pegunigalsidase alfa 的效果。
聚乙二醇化α-半乳糖苷酶A酶替代疗法(ERT)是一种治疗法布里病的聚乙二醇化α-半乳糖苷酶α,与其他每两周静脉注射一次的ERT(E2W)相比,它的血浆半衰期更长。BRIGHT(NCT03180840)是一项III期开放标签研究,研究对象是法布里病成人患者,他们曾接受阿加西酶α或贝塔E2W治疗≥3年,后改用每4周2毫克/千克的pegunigalsidase alfa(E4W)治疗52周。主要目标是评估安全性,包括治疗突发不良事件(TEAE)的数量。共有 30 名患者(24 名男性)入组,其中 23 名患者曾接受过阿加西酶 beta 治疗。在4周的给药间隔中,Pegunigalsidase alfa的血浆浓度始终高于定量下限。在 182 例 TEAEs 中,有 33 例(9 例患者)被认为与治疗有关;所有 TEAEs 均为轻度/中度。没有患者出现新的抗药抗体 (ADA)。在疗效分析中(n = 29),52 周内 eGFR 从基线变化的中位数(四分位数间距)为-1.9 (-5.9; 1.8) mL/min/1.73 m2(n = 28;男性 [n = 22]:-2.4 [-5.2; 3.2];女性 [n = 6]:-0.7 [-9.2; 2.0])。总体而言,eGFR 中位斜率为-1.9 (-8.3; 1.9) mL/min/1.73 m2/年(ADA 阴性 [n = 20]:-1.2 [-6.4; 2.6];ADA 阳性 [n = 9]:-8.4 [-11.6; -1.0])。女性的溶血-Gb3浓度较低且稳定,男性(9/24 ADA阳性)的溶血-Gb3浓度略有上升。BRIGHT 研究结果表明,2 毫克/千克 pegunigalsidase alfa E4W 对于病情稳定的成年法布里病患者耐受性良好。由于这项研究的患者人数较少,因此还需要更多的研究来证明聚甘道苷酶α E4W 的效果。医生在将每两周一次的 ERT 间隔延长至 E4W 时,应考虑到该临床试验之外的更多证据。带回的信息:每 4 周使用 2 毫克/千克 pegunigalsidase alfa 治疗可为法布里病患者提供一种新的治疗选择。
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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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