Jang Jun-Ho, Wong Raymond Siu Ming, Hartford Christopher, Pavani Rodrigo, Aurand Lisa, Nguyen Quang, Mohan Kosalai, Meagher Karoline, Sherman Steven, Rofail Diana, Perlee Lorah, Souttou Amal, Kelly Richard J
Department of Hematology-Oncology Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Republic of Korea.
Sir Y.K. Pao Centre for Cancer and Department of Medicine & Therapeutics Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong China.
EJHaem. 2025 Jul 24;6(4):e70095. doi: 10.1002/jha2.70095. eCollection 2025 Aug.
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, life-threatening disease associated with chronic intravascular hemolysis due to uncontrolled complement activation. PNH results in anemia with an increased risk of thrombosis, and often causes severe fatigue, and decreased physical function and health-related quality of life (QoL). We investigated the efficacy, safety, and patient-reported outcomes data of the combination of pozelimab (a fully human monoclonal antibody) and cemdisiran (an -acetylgalactosamine-conjugated small interfering ribonucleic acid) from a Phase 2 trial (NCT04811716) in patients with PNH who transitioned from pozelimab monotherapy.
In this randomized, open-label, Phase 2 study, patients were randomized (1:1) to one of two treatment arms; both arms received subcutaneous cemdisiran 200 mg every 4 weeks (Q4W) plus subcutaneous pozelimab 400 mg either Q4W (Arm 1) or every 2 weeks (Arm 2).
Twenty-four patients were treated with combination dosing. During the 28-week open-label treatment period (OLTP), 20 patients (83.3%) maintained control of lactate dehydrogenase (≤ 1.5 × upper limit of normal) at all timepoints. The majority of patients (92%) did not require a blood transfusion. While most patients (66.7%) experienced treatment-emergent adverse events, the majority of these events were mild to moderate in severity. No meningococcal infections, thrombotic events, or deaths were reported. The combination therapy maintained improvements in patient-reported fatigue, physical functioning, and QoL throughout the OLTP.
Combination treatment maintained adequate hemolysis control and was generally well tolerated. Administration of pozelimab Q2W did not improve disease control as compared to pozelimab Q4W.
ClinicalTrials.gov/NCT04811716.
阵发性睡眠性血红蛋白尿症（PNH）是一种极其罕见、危及生命的疾病，与补体不受控制激活导致的慢性血管内溶血相关。PNH会导致贫血，血栓形成风险增加，常引起严重疲劳、身体功能下降以及与健康相关的生活质量（QoL）降低。我们从一项2期试验（NCT04811716）中研究了泊泽利单抗（一种全人源单克隆抗体）和塞姆迪西然（一种与N - 乙酰半乳糖胺偶联的小干扰核糖核酸）联合用药在从泊泽利单抗单药治疗转换而来的PNH患者中的疗效、安全性及患者报告的结局数据。
在这项随机、开放标签的2期研究中，患者被随机（1:1）分配至两个治疗组之一；两组均每4周（Q4W）皮下注射200 mg塞姆迪西然，同时组1每4周（Q4W）皮下注射400 mg泊泽利单抗，组2每2周皮下注射400 mg泊泽利单抗。
24例患者接受了联合给药治疗。在28周的开放标签治疗期（OLTP）内，20例患者（83.3%）在所有时间点均维持乳酸脱氢酶控制在正常上限的1.5倍以内。大多数患者（92%）无需输血。虽然大多数患者（66.7%）经历了治疗中出现的不良事件，但这些事件大多为轻度至中度严重程度。未报告脑膜炎球菌感染、血栓形成事件或死亡病例。在整个OLTP期间，联合治疗维持了患者报告的疲劳、身体功能和QoL的改善。
联合治疗维持了充分的溶血控制，且总体耐受性良好。与每4周一次给药的泊泽利单抗相比，每2周一次给药并未改善疾病控制。
ClinicalTrials.gov/NCT04811716
