Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in 2 cohorts, 1 for patients with CAD and the other for those with wAIHA. In each cohort, patients were randomly assigned to receive pegcetacoplan 270 mg/d or 360 mg/d for up to 48 weeks. Safety end points included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy end points included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and functional assessment of chronic illness therapy (FACIT)-fatigue scale. Thirteen of 13 (100%) and 10 of 11 (91%) patients with CAD and wAIHA, respectively, experienced at least 1 TEAE. Ten patients had at least 1 serious AE; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90-3.00) and 1.7 g/dL (−1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective for patients with CAD and wAIHA. This trial was registered at www.ClinicalTrials.gov as #NCT03226678.

中文翻译：

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pegcetacoplan 治疗冷凝集素病和温抗体自身免疫性溶血性贫血的安全性和有效性


冷凝集素病 （CAD） 和温抗体自身免疫性溶血性贫血 （wAIHA） 是罕见的自身免疫性溶血性贫血，其特征是红细胞破坏，主要归因于补体激活导致血管内和血管外溶血。Pegcetacoplan 是一种皮下注射的 C3 靶向疗法，可能适用于治疗 CAD 和 wAIHA。在这项开放标签的 2 期研究中，对 2 个队列进行了分析，1 个针对 CAD 患者，另一个针对 wAIHA 患者。在每个队列中，患者被随机分配接受 pegcetacoplan 270 mg/d 或 360 mg/d，持续长达 48 周。安全终点包括治疗中出现的不良事件 （TEAE） 和特别关注的不良事件 （AESI） 的发生率和严重程度。疗效终点包括血红蛋白 （Hb） 、乳酸脱氢酶、网织红细胞绝对计数、结合珠蛋白、间接胆红素和慢性病治疗功能评估 （FACIT） -疲劳量表相对于基线的变化。13 例 CAD 和 wAIHA 患者中的 13 例 （100%） 和 11 例 （91%） 患者中的 10 例 （91%） 分别经历了至少 1 例 TEAE。10 例患者至少有 1 例严重 AE;没有人被认为与 Petcetaccoplan 有关。唯一与治疗相关的 AESI 是注射部位反应。Pegcetacoplan 在最初几周内增加了 Hb 水平，减少了溶血，并增加了 FACIT-疲劳量表评分;第 48 周时，CAD 和 wAIHA 总组相对于基线的中位（四分位距）Hb 变化分别为 2.4 （0.90-3.00） 和 1.7 g/dL （-1.40 至 2.90），溶血和 FACIT-疲劳量表评分保持改善。这项研究表明，pegcetacoplan 通常耐受性良好，并表明它对 CAD 和 wAIHA 患者有效。 该试验在 www.ClinicalTrials.gov 注册为 #NCT03226678。