A Potential Long-Acting LDL-Cholesterol-Lowering PCSK9 Monoclonal Antibody: 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 600 mg tafolecimab subcutaneously, 75 or 450 mg intravenously, or placebo. Sixty patients with hypercholesterolemia (phase 1b) were randomized to receive 75 or 140 mg tafolecimab every 2 weeks, 300 or 420 mg every 4 weeks, or 450 or 600 mg every 6 weeks subcutaneously or placebo for 12 weeks. 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).

Keywords: AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; HDL-C, high-density lipoprotein-cholesterol; IV, intravenously; LDL cholesterol; LDL-C, low-density lipoprotein-cholesterol; PCSK9; PCSK9, proprotein convertase subtilisin/kexin type 9; QxW, every x weeks; SC, subcutaneously; TEAE, treatment-emergent adverse effect; hypercholesterolemia; tafolecimab.

Conflict of interest statement

This study was sponsored by Innovent Biologics and funded by National Science and Technology Major Projects (2019ZX09732-001). Drs Qian, Deng, and H. Li are employees of Innovent Biologics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

© 2021 The Authors.

Figures

Figure 1

Effects of Tafolecimab on LDL-C Levels Percentage changes from baseline in LDL-C levels in the (A) phase 1a and (B) phase 1b studies. Error bars indicate standard error (SE). IV = intravenously; LDL-C = low-density lipoprotein cholesterol; Q2W, Q4W, Q6W = every 2, 4, 6 weeks; SC = subcutaneously.