Recaticimab Monotherapy for Nonfamilial Hypercholesterolemia and Mixed Hyperlipemia: The Phase 3 REMAIN-1 Randomized Trial.

Autor:	Xu M; Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Wang Z; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China., Zhang Y; Department of Cardiology, The Third Hospital of Changsha, Changsha, China., Liu Y; Department of Cardiology, Tianjin Fourth Central Hospital, Tianjin, China., Huang R; Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China., Han X; Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, China., Yao Z; Department of Cardiology, Tianjin Union Medical Center, Tianjin, China., Sun J; Department of Endocrinology, Huadong Hospital Affiliated to Fudan University, Shanghai, China., Tian F; Department of Endocrinology and Diabetes, Cangzhou Hospital of Integrated TCM-WM, Cangzhou, China., Hu X; Department of Cardiology, Shijiazhuang General Hospital, Shijiazhuang, China., Ma L; Department of Cardiovascular Medicine, Shulan (Hangzhou) Hospital, Hangzhou, China., Lai C; Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, China., Zhang X; Department of Cardiovascular Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China., Sheng J; Department of Cardiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China., Han Q; Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, China., Jin C; Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, China., Luo L; Department of Cardiovascular Medicine, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, China., Zhao R; Department of Cardiovascular Medicine, Baotou Central Hospital, Baotou, China., Li L; Department of Cardiovascular Medicine, Guangdong Provincial People's Hospital, Guangzhou, China., Xu B; Department of Cardiology, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Yin D; Department of Cardiology, The First People's Hospital of Lianyungang, Lianyungang, China., Luo S; Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Ge X; Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China., Liu Z; Department of Cardiovascular, Nanyang Central Hospital, Nanyang, China., Yang P; Department of Cardiology, China-Japan Union Hospital of Jinlin University, Changchun, China., Huang Z; Department of Cardiovascular, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Li T; Department of Cardiovascular, First Affiliated Hospital of Hainan Medical College, Haikou, China., Feng W; Department of Cardiovascular, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, China., Wu Y; Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China., Ling Z; Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China., Ma L; Department of Cardiology, Anhui Provincial Hospital, Hefei, China., Lv C; Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China., Deng C; Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China., Wei W; Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China., Wang Y; Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China., Yan L; Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: hfxyl@163.net., Ge J; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: jbge@zs-hospital.sh.cn.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Cardiology [J Am Coll Cardiol] 2024 Nov 12; Vol. 84 (20), pp. 2026-2036. Date of Electronic Publication: 2024 Oct 09.
DOI:	10.1016/j.jacc.2024.07.035
Abstrakt:	Background: Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have been used to reduce the level of low-density lipoprotein cholesterol (LDL-C), but require either biweekly or monthly dosing frequency. Recaticimab is a new humanized monoclonal antibody selectively targeting PCSK9, with long-acting characteristic. Objectives: The purpose of this study was to assess the efficacy and safety of recaticimab monotherapy in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk, and to explore different dosing strategies to provide patients with flexible administration options. Methods: This was a randomized, double-blind, placebo-controlled, phase 3 study conducted at 59 sites in China. Patients with fasting LDL-C ≥2.6 to <4.9 mmol/L, fasting triglyceride ≤5.6 mmol/L, and 10-year ASCVD risk score <10% were randomly assigned (2:2:2:1:1:1) to receive subcutaneous injections of recaticimab at 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg every 12 weeks (Q12W), or matching placebo, on background lipid-lowering diet. Primary endpoint was percentage change in LDL-C from baseline to week 12 for 150 mg Q4W and 450 mg Q12W and to week 16 for 300 mg Q8W. Results: A total of 703 patients underwent randomization and received recaticimab (n = 157, 156, and 155 for 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W, respectively) or placebo (n = 78, 79, and 78, respectively). Compared with placebo, recaticimab further reduced LDL-C by 49.6% (95% CI: 44.2%-54.9%) at 150 mg Q4W, 52.8% (95% CI: 48.3%-57.2%) at 300 mg Q8W, and 45.0% (95% CI: 41.0%-49.0%) at 450 mg Q12W (P < 0.0001 for all comparisons). Safety with recaticimab was comparable to placebo. After 12 or 16 weeks of treatment, patients who received recaticimab continued treatment until week 24, whereas those allocated to placebo were switched to recaticimab treatment with the same dosing strategy. Both 24-week recaticimab and 12- or 8-week recaticimab switched from placebo were effective. With 24 weeks of recaticimab treatment, the most common treatment-related adverse event was injection site reaction (n = 23 [4.9%]). Conclusions: Recaticimab monotherapy yielded significant LDL-C reductions and showed comparable safety vs placebo in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate ASCVD risk, even with an infrequent dosing interval up to Q12W. Competing Interests: Funding Support and Author Disclosures This trial was sponsored by Jiangsu Hengrui Pharmaceuticals. Drs Lv, Deng, Wei, and Y. Wang are employed by Jiangsu Hengrui Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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