PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study

Mingtong Xu, Xiaoxue Zhu, Junyan Wu, Yuling Zhang, Dong Zhao, Xuhong Wang, Yanhua Ding, Yu Cao, Chengqian Li, Wei Hu, Jianlong Sheng, Zhu Luo, Zeqi Zheng, Jinfang Hu, Jianying Liu, Xiaoyang Zhou, Aizong Shen, Xiaomei Ding, Yongdong Zhang, Yonggang Zhao, Yijing Li, Sheng Zhong, Shimin An, Jianjun Zou, Li Yan, Mingtong Xu, Xiaoxue Zhu, Junyan Wu, Yuling Zhang, Dong Zhao, Xuhong Wang, Yanhua Ding, Yu Cao, Chengqian Li, Wei Hu, Jianlong Sheng, Zhu Luo, Zeqi Zheng, Jinfang Hu, Jianying Liu, Xiaoyang Zhou, Aizong Shen, Xiaomei Ding, Yongdong Zhang, Yonggang Zhao, Yijing Li, Sheng Zhong, Shimin An, Jianjun Zou, Li Yan

Abstract

Background: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia.

Methods: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule).

Results: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase.

Conclusion: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo.

Trial registration: ClinicalTrials.gov , number NCT03944109.

Keywords: Hypercholesterolemia; Infrequent administration; PCSK9; Recaticimab.

Conflict of interest statement

YL, SZ, SA, and JZ reported being employed at Jiangsu Hengrui Pharmaceuticals. No other disclosures were reported.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study flow. *2, 2, 2, 4, 4, and 4 patients were assigned to receive placebo at a dose and frequency of 75 mg Q4W, 150 mg Q4W, 150 mg Q8W, 300 mg Q8W, 300 mg Q12W, and 450 mg Q12W, respectively
Fig. 2
Fig. 2
Percentage change in LDL-C during treatment. Mean percentage changes (standard error) in LDL-C from baseline to end of treatment (i.e., at week 16 for patients receiving treatment Q4W and Q8W and at week 24 for patients receiving treatment Q12W) are shown. LDL-C low-density lipoprotein cholesterol

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