Abstract 19469: PBI-4050 Reduces Cardiovascular Biomarkers in Type II Diabetic Patients With Metabolic Syndrome
Introduction: Patients suffering of metabolic syndrome and type II diabetes with elevated blood levels of pentraxine-3 and resistin have been shown to have a significantly increased incidence of cardiovascular events. PBI-4050 is an orally active drug candidate with anti-fibrotic efficacy in multiple preclinical models of fibrosis in kidney, liver, lung, heart and pancreas. More specifically, PBI-4050 has been shown to significantly reduce fibrosis in the heart without unduly affecting hemodynamic performance in preclinical models such as myocardial infarction and suprarenal banding of the aorta. PBI-4050, via the same mechanism of action, was also shown to protect against pancreatic fibrosis by reducing macrophage and lymphocyte infiltration, ER stress and increasing autophagy.
Methods: A phase II, open label, single center, single arm study in twenty type II diabetes patients with metabolic syndrome was undertaken. The objectives were to evaluate the efficacy safety and tolerability of PBI-4050 following oral administration of 800 mg once daily for 12 weeks, and to demonstrate pharmacological activity and translation of efficacy from preclinical studies to humans by monitoring early evidence of changes in cardiovascular and renal disorders biomarkers as well as the effect on HbA1c as an indirect measurement of pancreatic function.
Results: PBI-4050 was demonstrated to be safe and well tolerated without SAEs. PBI-4050 treatment reduced pentraxine-3 and resistin in blood (p<0.01) and Il-18 in urine. PBI-4050 treatment also reduced HbA1c (average ΔHbA1c of -0.80, p=0.003 with HbA1c baseline of >7.5%, average ΔHbA1c of -1%, p=0.003 with HbA1c baseline of >7.5%,) in twenty patients.
Conclusions: PBI-4050 was safe and well tolerated in type II diabetic patients with metabolic syndrome. PBI-4050 was efficacious in reducing cardiovascular biomarkers pentraxine-3 and resistin, renal biomarker IL-18 as well as HbA1c. These results demonstrate that PBI-4050 may be an efficacious therapy for patients with metabolic syndrome patients and type II diabetes, and with a high risk of developing cardiovascular events.
- Cardiovascular disease prevention
- Inflammation and inflammatory markers
Author Disclosures: P. Laurin: Employment; Significant; ProMetic BioSciences Inc.. Ownership Interest; Significant; ProMetic Life Sciences Inc. B. Grouix: Employment; Significant; ProMetic BioSciences Inc.. Ownership Interest; Modest; ProMetic Life Sciences Inc. A. Laverdure: Employment; Significant; ProMetic BioSciences Inc.. Ownership Interest; Modest; ProMetic Life Sciences Inc. B. Zacharie: Employment; Significant; ProMetic BioSciences Inc.. Ownership Interest; Modest; ProMetic Life Sciences Inc. L. Gagnon: Employment; Significant; ProMetic BioSciences Inc.. Ownership Interest; Modest; ProMetic Life Sciences Inc..
- © 2016 by American Heart Association, Inc.