Recaticimab as Add-On Therapy to Statins for Nonfamilial Hypercholesterolemia: The Randomized, Phase 3 REMAIN-2 Trial

J Am Coll Cardiol. 2024 Nov 12;84(20):2037-2047. doi: 10.1016/j.jacc.2024.09.012.

Yihong Sun ¹, Qiang Lv ¹, Yuhan Guo ², Zhifang Wang ³, Rongjie Huang ⁴, Xiaohong Gao ⁵, Yajun Han ⁶, Zhuhua Yao ⁷, Mingqi Zheng ⁸, Suxin Luo ⁹, Yue Li ¹⁰, Xiang Gu ¹¹, Yumin Zhang ¹², Junkui Wang ¹³, Lang Hong ¹⁴, Xueping Ma ¹⁵, Guohai Su ¹⁶, Jianlong Sheng ¹⁷, Chunlin Lai ¹⁸, Aidong Shen ¹⁹, Mian Wang ²⁰, WeiHua Zhang ²¹, Shaorong Wu ²², Zeqi Zheng ²³, Juxiang Li ²⁴, Tingyan Zhong ², Ying Wang ², Liu He ¹, Xin Du ¹, Chang-Sheng Ma ²⁵

Affiliations

1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
2 Jiangsu Hengrui Pharmaceuticals, Co Ltd, Shanghai, China.
3 Department of Cardiology, Xinxiang Central Hospital, Xinxiang, China.
4 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
5 Department of Cardiology, Beijing Pinggu Hospital, Beijing, China.
6 Department of Geriatric Cardiology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China.
7 Department of Cardiology, Tianjin Union Medical Center, Tianjin, China.
8 Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
9 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
10 Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
11 Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, China.
12 Department of Cardiology, The Third Hospital of Changsha, Changsha, China.
13 Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, China.
14 Department of Cardiology, The Jiangxi Provincial People's Hospital, Nanchang, China.
15 Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, China.
16 Department of Cardiology, Jinan Central Hospital/Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
17 Department of Cardiology, The Second Hospital of Anhui Medical University, Hefei, China.
18 Department of Cardiology, Shanxi Provincial People's Hospital, Taiyuan, China.
19 Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
20 Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
21 Department of Cardiology, First Bethune Hospital of Jilin University, Changchun, China.
22 Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
23 Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
24 Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
25 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address: [email protected].

PMID: 39505412 DOI: 10.1016/j.jacc.2024.09.012

Abstract

Background: Currently available antiproprotein convertase subtilisin/kexin type 9 monoclonal antibodies can effectively decrease low-density lipoprotein Cholesterol (LDL-C) levels, but require frequent dosing. Recaticimab is a novel humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9. In a phase 1b/2 trial, recaticimab as add-on to stable statins showed robust LDL-C reduction with a dosing interval up to every 12 weeks (Q12W) in patients with hypercholesterolemia.

Objectives: REMAIN-2 (REcaticiMab Add-on therapy In patients with Nonfamilial hypercholesterolemia) aimed to assess the efficacy and safety of 48-week treatment with recaticimab as add-on therapy to statins in nonfamilial hypercholesterolemia.

Methods: REMAIN-2 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. During the run-in period, patients received stable moderate or high-intensity statin, with or without Cholesterol absorption inhibitors (ezetimibe) or fenofibrate, for ≥4 weeks. Patients with an LDL-C of ≥1.8 mmol/L (if with atherosclerotic Cardiovascular Disease [ASCVD]) or ≥2.6 mmol/L (if without ASCVD) were then randomized (2:2:2:1:1:1) to receive recaticimab 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg Q12W, or matching placebo injections (Q4W, Q8W, or Q12W) for 48 weeks. The primary efficacy endpoint was percentage change from baseline to week 24 in LDL-C level.

Results: A total of 689 randomly assigned patients received treatment (mean age, 55.8 years; male, 64.4%; ASCVD history, 69.5%; concomitant ezetimibe, 11.2%; mean baseline LDL-C, 2.8 mmol/L). Percentage change in LDL-C from baseline to week 24 was significantly more pronounced with recaticimab vs placebo (P < 0.0001), with least-squares mean differences of -62.2% (95% CI: -67.0% to -57.4%), -59.7% (95% CI: -65.0% to -54.4%), and -53.4% (95% CI: -58.7% to -48.2%) for the 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W regimens, respectively. The decreases in LDL-C with recaticimab were maintained through week 48. Secondary lipid variables, including non-high-density lipoprotein Cholesterol, Apolipoprotein B, and lipoprotein(a) also favored the recaticimab groups. During the treatment period, the incidence of treatment-related adverse events (28.5% vs 26.6%) and serious treatment-related adverse events (0.4% vs 0.4%) was similarly low in both the recaticimab and placebo groups.

Conclusions: Recaticimab as add-on to stable statin therapy significantly decreased LDL-C levels at week 24 and sustained the decreases through week 48, providing a novel therapeutic alternative with a dosing interval of up to every 12 weeks in patients with nonfamilial hypercholesterolemia.

Keywords

LDL; PCSK9; cholesterol; lipoproteins; nonfamilial hypercholesterolemia; recaticimab.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-P99822

Recaticimab

99.71%, PCSK9 Inhibitor

PCSK9

Metabolic Disease

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