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Cerenis Therapeutics Announces the Results of the LOCATION StudyCerenis Therapeutics (Paris:CEREN) (FR0012616852 - CEREN), an international biopharmaceutical company dedicated to the discovery and development of innovative HDL therapies ("good cholesterol") for treating cardiovascular and metabolic diseases, today announced the results of the LOCATION clinical study, which evaluated the selectivity of CER-001, an HDL mimetic made of recombinant human apolipoprotein A-I (apoA-I) and phospholipids, for carotid plaques in patients with advanced atherosclerotic disease. The LOCATION study provides the first evidence of CER-001 selective targeting of atherosclerotic plaques in patients, and of the role of plaque permeability in plaque penetration by an HDL mimetic. The study evaluated 8 patients with >50% atherosclerotic stenosis of the carotid artery who received an infusion of CER-001 (3 mg/kg body weight) labeled with Zirconium-89, a tracer suited for PET/CT imaging, to determine the extent to which CER-001 targets and penetrates atherosclerotic plaques and the effect on cholesterol efflux, a marker which is inversely related to the incidence of adverse cardiovascular events1.
Using serial PET/CT imaging, the investigators were able to show that plaque uptake of CER-001 increased significantly 24 hours after infusion (14%), and remained increased up to 48 hours (12%). This is the first demonstration of plaque penetration by CER-001 in patients with atherosclerotic disease.
By looking at specific segments of the carotid arteries with and without atherosclerotic plaques, the investigators were ableto show that the uptake of CER-001 was higher in segments with plaques than in non-plaque segments demonstrating that infused CER-001 preferentially enters atherosclerotic plaques in patients. Using an imaging technique that allows the evaluation of the permeability of atherosclerotic plaques, they were also able to show that the extent to which CER-001 enters the plaque is determined by the plaque's permeability. This observation supports the concept and may be particularly relevant for the selection of patients most likely to benefit from apoA-I-containing HDL-mimetic therapy based on plaque permeability.
In addition, by collecting serial blood samples, the investigators showed that one hour after CER-001 infusion plasma-mediated cholesterol efflux increased by 13.8% and mean plasma apoA-I levels increased by 9.9 mg/dL. Both apoA-I levels and cholesterol efflux capacity returned to baseline values after 24 hours. The results of the LOCATION study are consistent with the findings of the CER-001 clincial program to date, which have shown that CER-001 effectively mobilises cholesterol and regress atherosclerosis. The findings validate plaques targeting with CER-001 at the dose being investigated in the planned CARAT study (NCT02484378), a double-blind, placebo-controlled, phase II study assessing the effect of CER-001 on atherosclerosis regression in patients with acute coronary syndrome (ACS (News - Alert)). Professor Erik Stroes, Principal Investigator of the LOCATION study commented that: "The LOCATION study confirms for the first time the targeting of atherosclerotic plaques by apoA-I containing HDL mimetics in humans, an effect only previously observed in experimental models of atherosclerotic disease. Targeting of atherosclerotic plaques was observed at a dose of 3 mg/kg, the dose that will be used in the Phase II CARAT clinical trial in post-ACS patients the first of whom will be enrolled into the trial this quarter. Encouragingly, the LOCATION study has also shown that CER-001 targeting of atherosclerotic plaques is associated with an increased cholesterol efflux capacity, a marker that was recently demonstrated by Daniel J. Rader and his team at University of Pennsylvania to be predictive of a reduction in cardiovascular-related mobidity and mortality. Our results are also consistent with the observed reduction in atherosclerosis shown in patients with HDL deficiencies, in patients with homozygous familial hypercholesterolemia, and in post-ACS patients. We will be submitting the full results from the LOCATION study to a peer-reviewed journal shortly". Download the full pdf file on http://cerenis.com/en/media-en/press-releases
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