HDL mimetic did not reach primary endpoint of atherosclerosis regression
An HDL-mimetic therapy failed to reach its primary endpoint in post-Acute Coronary Syndrome (ACS) patients in the Phase IIb CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis REgression?) study. This trial recruited ~500 ACS patients to test the agent CER-001 (Cerenis Therapeutics) in its capacity to reduce the lipid-carrying plaque in the arteries (as measured by intravascular ultrasound (IVUS). CHI-SQUARE is a double-blind, randomised, placebo-controlled dose-ranging study.
CER-001 did not regress coronary atherosclerotic plaque significantly differently from placebo. CER-001 is the next agent in a series of HDL-therapies that failed to show clinical benefit.
A dose-dependent mobilisation of cholesterol was seen in post-ACS patients with a potency consistent with the prior Phase I study in healthy volunteers. Reduction of Total Atheroma Volume (TAV) was however not significantly different from placebo in the modified Intention to Treat (mITT) population (n= 417).
One of three doses in the CER-001 study did however achieve ‘nominal statistical significance vs. placebo for TAV and percent atheroma volume, in the modified Per Protocol population (295 patients). Thus, Jean-Louis Dasseux, PhD, MBA, and CEO of Cerenis, concludes that CER-001 warrants further study: “In all preclinical and clinical studies to date, CER-001 has been shown to perform the functions of natural HDL and the steps of the Reverse Lipid Transport Pathway with a high degree of potency. We remain confident that CER-001 has the potential to be demonstrated to be a clinically valuable pre-beta HDL mimetic, and that CER-001 will be shown to offer an important benefit for patients suffering from cardiovascular disease.”
Press release Cerenis Therapeutics, 2 January 2014