Tafolecimab provided significant, durable decreases in low-density lipoprotein cholesterol (LDL-C) levels when administered at both 450 mg every 4 weeks or 600 mg every 6 weeks among patients with non-familial hypercholesterolemia, according to findings presented at the American Heart Association Scientific Sessions 2022.
“Currently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies demonstrated robust LDL-C-lowering efficacy at doses up to 420 mg monthly, while longer dosing intervals are largely unexplored,” the researchers wrote. “We assessed the efficacy and safety of tafolecimab, a potential long-acting fully human PCSK9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia.”
The investigators randomly assigned patients 2:2:1:1 to receive subcutaneous tafolecimab 450 mg every 4 weeks (Q4W), tafolecimab 600 mg every 6 weeks (Q6W), placebo Q4W, or placebo Q6W for 48 weeks. The percentage change from baseline to week 48 in LDL-C levels served as the primary endpoint. Secondary endpoints included the proportion of patients reaching LDL-C reductions of greater than or equal to 50%, an LDL-C of less than 1.8 mmol/L, and an LDL-C of less than 1.4 mmol/L.
Tofalecimab Reduces LDL-C With Favorable Safety Profile
The study included 618 patients (mean LDL-C level, 2.85 mmol/L). Of these patients, 9.3% were being treated with ezetimibe and 72.8% were at very high cardiovascular risk. In total, 614 patients were treated with at least one dose of the study drug, and 92.5% of these patients finished the study.
At both dose levels, tafolecimab resulted in significant decreases in LDL-C levels, and significantly more patients receiving tafolecimab achieved an LDL-C decrease of greater than or equal to 50%, LDL-C levels of less than 1.8 mmol/L, and LDL-C levels of less than 1.4 mmol/L compared with corresponding placebo groups. The researchers observed significant declines in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) with tafolecimab versus placebo at week 48. The most frequently reported treatment-emergent adverse events included upper respiratory tract infection, urinary tract infection, and hyperuricemia.
“Tafolecimab administered at either 450 mg Q4W or 600 mg Q6W yielded significant and durable reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with non-familial hypercholesterolemia,” the investigators wrote.