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

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

  • BMC Med. 2022 Jan 18;20(1):13. doi: 10.1186/s12916-021-02208-w.
Mingtong Xu # 1,  Xiaoxue Zhu # 2,  Junyan Wu 3,  Yuling Zhang 4,  Dong Zhao 5,  Xuhong Wang 5,  Yanhua Ding 2,  Yu Cao 6,  Chengqian Li 7,  Wei Hu 8,  Jianlong Sheng 9,  Zhu Luo 10,  Zeqi Zheng 11,  Jinfang Hu 12,  Jianying Liu 13,  Xiaoyang Zhou 14,  Aizong Shen 15,  Xiaomei Ding 16,  Yongdong Zhang 17,  Yonggang Zhao 18,  Yijing Li 19,  Sheng Zhong 19,  Shimin An 19,  Jianjun Zou 19,  Li Yan 20
Affiliations

Affiliations

  • 1 Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, China.
  • 2 Phase I Clinical Trials Unit, The First Hospital of Jilin University, Changchun, China.
  • 3 Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 4 Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 5 Endocrinology Center, Capital Medical University, Beijing Luhe Hospital, Beijing, China.
  • 6 Phase I Clinical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • 7 Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • 8 Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China.
  • 9 Department of Cardiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 10 Department of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
  • 11 Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 12 Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 13 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 14 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 15 Department of Pharmacy, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
  • 16 Department of Cardiology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
  • 17 Department of Pharmacy, Chenzhou First People's Hospital, Chenzhou, China.
  • 18 Department of Emergency Medicine, Chenzhou First People's Hospital, Chenzhou, China.
  • 19 Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China.
  • 20 Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, China. [email protected].
  • # Contributed equally.
PMID: 35039035 DOI: 10.1186/s12916-021-02208-w
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.

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