Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial.

BACKGROUND

Tafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia.

OBJECTIVES

The purpose of this study was to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia.

METHODS

Patients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels.

RESULTS

A total of 303 patients were enrolled and received at least 1 dose of tafolecimab (n = 205) or placebo (n = 98). The least squares mean percent change in LDL-C level from baseline to week 12 was -68.9% (SE 1.4%) in the tafolecimab group and -5.8% (1.8%) in the placebo group (difference: -63.0%; [95% CI: -66.5% to -59.6%];  < 0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than did those in the placebo group (all  < 0.0001). Furthermore, tafolecimab markedly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. During the double-blind treatment period, the most commonly reported adverse events included urinary tract infection (5.9% with tafolecimab vs 4.1% with placebo) and hyperuricemia (3.4% vs 4.1%).

CONCLUSIONS

Tafolecimab was safe and showed robust lipid-lowering efficacy in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. (A Study of IBI306 in Participants With Hypercholesterolemia; NCT04709536).