Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes: Phase 1 Results

Area of Science:

• Cardiovascular Medicine
• Immunology
• Pharmacology

Background:

• Atherosclerosis involves inflammatory and lipid risk factors.
• Blockade of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) presents a therapeutic strategy.
• MEDI6570 is a monoclonal antibody designed to block LOX-1.

Purpose of the Study:

• To evaluate the safety and tolerability of MEDI6570 in a first-in-human study.
• To assess target engagement by measuring soluble LOX-1 levels.
• To explore the pharmacokinetic profile and effect on coronary plaque volume.

Main Methods:

• Phase 1, placebo-controlled, randomized study (NCT03654313) with 88 patients with type 2 diabetes.
• Single and multiple ascending doses of MEDI6570 or placebo administered over 3 months.
• Safety, pharmacokinetics, immunogenicity, soluble LOX-1 levels, and coronary plaque volume were assessed.

Main Results:

• MEDI6570 was safe and well-tolerated across all dose cohorts.
• Nonlinear pharmacokinetics observed, with half-life increasing with dose.
• Significant, dose-dependent reductions in soluble LOX-1 levels were achieved (>66% at 4 weeks, up to 82.96% at 10 weeks).
• A trend towards regression in noncalcified plaque volume was noted but not statistically significant.

Conclusions:

• MEDI6570 demonstrates a favorable safety profile and tolerability.
• The drug effectively suppresses soluble LOX-1 in a dose-dependent manner.
• Pharmacokinetic data support a potential once-monthly dosing regimen for future studies.