Barratt Jonathan, Barbour Sean J, Brenner Robert M, Cooper Kerry, Wei Xuelian, Eren Necmi, Floege Jürgen, Jha Vivekanand, Kim Sung Gyun, Maes Bart, Phoon Richard K S, Singh Harmeet, Tesař Vladimír, Lafayette Richard
College of Medicine Biological Sciences and Psychology, University of Leicester, Leicester, United Kingdom.
Division of Nephrology, The University of British Columbia, Vancouver, British Columbia, Canada.
J Am Soc Nephrol. 2025 Apr 1;36(4):679-687. doi: 10.1681/ASN.0000000541. Epub 2024 Oct 26.
Participants who completed a 36-week double-blind study of atacicept were eligible for a 60-week, open-label extension study. Atacicept 96-week treatment resulted in sustained reductions in galactose-deficient IgA1, hematuria, and urine protein-creatinine ratio. The slope of the eGFR was similar to that observed in the general population without kidney disease.
B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in the pathogenesis of IgA nephropathy. Atacicept is a novel fully humanized fusion protein, self-administered at home by subcutaneous injection, that binds and inhibits BAFF and APRIL. By inhibiting BAFF and APRIL, atacicept targets the underlying B-cell–mediated pathogenesis driving disease progression. This study evaluated the long-term efficacy and safety of atacicept in patients with IgA nephropathy over 96 weeks.
Participants with IgA nephropathy who received atacicept (25, 75, or 150 mg) or placebo in a 36-week phase 2b, randomized, blinded trial were enrolled in an open-label extension study and received atacicept 150 mg for an additional 60 weeks. Key efficacy outcomes were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, urine protein-creatinine ratio (UPCR), and eGFR over 96 weeks. Long-term safety data were also evaluated.
There were 113 participants (67 [59%] male; 46 [41%] female) who ranged in age from 18 to 67 years who received ≥1 atacicept dose. Over 96 weeks, safety data demonstrated that atacicept was generally well tolerated. There were also sustained reductions (mean±SEM) in Gd-IgA1 (−66%±2%), percentage of participants with hematuria (−75%; 95% confidence intervals, −87 to −59; in participants with baseline hematuria), and UPCR (−52%±5%). The mean annualized slope of eGFR was −0.6±0.5 ml/min per 1.73 m through 96 weeks.
Atacicept was well tolerated over the duration of the study. Atacicept treatment reduced Gd-IgA1, hematuria, and UPCR with stabilization of eGFR through 96 weeks.
: Atacicept in Subjects with IgA Nephropathy (ORIGIN 2), NCT04716231.
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完成了一项为期36周的阿他西普双盲研究的参与者有资格参加一项为期60周的开放标签扩展研究。阿他西普96周的治疗导致半乳糖缺陷型IgA1、血尿和尿蛋白肌酐比值持续降低。估算肾小球滤过率（eGFR）的斜率与无肾脏疾病的普通人群中观察到的斜率相似。
B细胞活化因子（BAFF）和增殖诱导配体（APRIL）在IgA肾病的发病机制中起关键作用。阿他西普是一种新型的完全人源化融合蛋白，可在家中自行皮下注射，它能结合并抑制BAFF和APRIL。通过抑制BAFF和APRIL，阿他西普针对驱动疾病进展的潜在B细胞介导的发病机制。本研究评估了阿他西普在IgA肾病患者中96周的长期疗效和安全性。
在一项为期36周的2b期随机双盲试验中接受阿他西普（25、75或150mg）或安慰剂治疗的IgA肾病参与者被纳入一项开放标签扩展研究，并接受150mg阿他西普额外治疗60周。关键疗效指标是96周内半乳糖缺陷型IgA1（Gd-IgA1）、血尿参与者百分比、尿蛋白肌酐比值（UPCR）和eGFR的变化。还评估了长期安全性数据。
有113名参与者（67名[59%]男性；46名[41%]女性），年龄在18至67岁之间，接受了≥1剂阿他西普。在96周内，安全性数据表明阿他西普总体耐受性良好。Gd-IgA1（-66%±2%）、血尿参与者百分比（-75%；95%置信区间，-87至-59；基线有血尿的参与者）和UPCR（-52%±5%）也持续降低。至96周时，eGFR的年均斜率为-0.6±0.5ml/min/1.73m²。
在研究期间，阿他西普耐受性良好。阿他西普治疗降低了Gd-IgA1、血尿和UPCR，并使eGFR在96周内保持稳定。
IgA肾病患者的阿他西普（ORIGIN 2），NCT04716231。
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