The Lancet Regional Health. Western Pacific (Dec 2023)

Tafolecimab in Chinese patients with non-familial hypercholesterolemia (CREDIT-1): a 48-week randomized, double-blind, placebo-controlled phase 3 trialResearch in context

  • Yong Huo,
  • Beijian Chen,
  • Qiufang Lian,
  • Shuqing Wang,
  • Lu Liu,
  • Di Lu,
  • Yanling Qu,
  • Guanzhong Zheng,
  • Lipeng Li,
  • Yuan Ji,
  • Guotian Yin,
  • Wenjun Huang,
  • Ying Xie,
  • Xinchun Yang,
  • Xiufang Gao,
  • Pei An,
  • Fengtai Xue,
  • Haoyu Li,
  • Huan Deng,
  • Li Li,
  • Lijuan Pei,
  • Lei Qian

Journal volume & issue
Vol. 41
p. 100907

Abstract

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Summary: Background: Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Methods: Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L or non-FH patients with screening LDL-C level ≥3.4 mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450 mg Q4W, tafolecimab 600 mg Q6W, placebo 450 mg Q4W, or placebo 600 mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Findings: A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n = 411) or placebo (n = 203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]: −65.0% [97.5% CI: −70.2%, −59.9%] for 450 mg Q4W; −57.3% [97.5% CI: −64.0%, −50.7%] for 600 mg Q6W; both P < 0.0001). Significantly more patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C < 1.8 mmol/L, and LDL-C < 1.4 mmol/L than placebo group at both dose regimens (all P < 0.0001). Furthermore, tafolecimab significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. The most commonly-reported treatment emergent adverse events in the tafolecimab groups included upper respiratory infection, urinary tract infection and hyperuricemia. Interpretation: Tafolecimab dosed at 450 mg Q4W and 600 mg Q6W was safe and showed superior lipid-lowering efficacy versus placebo, providing a novel treatment option for Chinese hypercholesterolemia patients. Funding: This study was sponsored by Innovent Biologics, Inc.

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