A Potential Long-Acting LDL-Cholesterol-Lowering PCSK9 MonoclonalAntibody: Randomized, Placebo-Controlled Phase 1 Studies.

Abstract

The aim of the studies was to evaluate the safety, tolerability, and efficacy of tafolecimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, in Chinese healthy volunteers and patients with hypercholesterolemia. Fifty-eight healthy volunteers (phase 1a) were randomized to receive a single dose of 25, 75, 150, 300, 450, or 600mg tafolecimab subcutaneously, 75 or 450mg intravenously, or placebo. Sixty patients with hypercholesterolemia (phase 1b) were randomized to receive 75 or 140mg tafolecimab every 2weeks, 300 or 420mg every 4weeks, or 450 or 600mg every 6weeks subcutaneously or placebo for 12weeks. Tafolecimab was well tolerated. Adverse events in both studies were either mild or moderate. In the phase 1a study, a single dose of tafolecimab reduced low-density lipoprotein-cholesterol (LDL-C) levels up to 72% in healthy volunteers. In the phase 1b study, tafolecimab reduced LDL-C levels up to 71.6% and by more than 50% consistently to week 12 for all tafolecimab dose regimens. Tafolecimab is a safe PCSK9 monoclonal antibody with significant and potential long-acting LDL-C-lowering effect. (Single Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Healthy Subjects; NCT03366688) (Multiple Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Chinese Patients With Hypercholesterolemia; NCT03815812).