HDL Mimetic Fails to Regress Plaque in CHI-SQUARE ACS Trial

Shelley Wood

January 03, 2014

TOULOUSE, FRANCE AND ANN ARBOR, MI — A phase 2b trial of CER-001 (Cerenis Therapeutics), an engineered complex of recombinant human apolipoprotein A1 (apoA1) (the major structural protein of HDL), has failed to show that the agent can reduce total atheroma volume in patients with acute coronary syndrome (ACS), the company has announced[1].

Cerenis Therapeutics announced the results of the Can HDL Infusions Significantly Quicken Atherosclerosis Regression? (CHI-SQUARE) study January 2, 2014.

CER-001 is intended to mimic natural, nascent HDL (also known as pre-beta HDL) and to transiently increase apoA1 and the number of HDL particles to accelerate reverse lipid transport. CHI-SQUARE, led by Dr Jean-Claude Tardif (Montreal Heart Institute, QC) randomly assigned 507 patients with ACS at one of 53 centers to either placebo or ascending doses of CER-001 (1:3 randomization), given by weekly infusion for six weeks.

As a Cerenis press release noted, intravascular ultrasound (IVUS) scans conducted three weeks after the last dose of the study drug showed that CER-001 infusions reduced total atheroma volume from baseline (a statistically significant difference), but the change was not significantly different from the change from baseline seen in placebo-treated patients.

Mobilization of cholesterol did appear to be dose-dependent, and one of the doses appeared to demonstrate significant benefits in cholesterol transport, as measured by atheroma volume, prompting the company to state that it is conducting a "detailed review to further understand these results and to determine the best path forward."

Of note, several other companies have HDL mimetics in development. Late last year at the American Heart Association 2013 Scientific Sessions, two HDL mimetics—CSL-112 (CSL Limited) and ETC-1002 (Esperion)—showed positive results in phase 2a studies (both smaller than the CHI-SQUARE study and with biomarker end points). The Medicines Company, meanwhile, is developing MDCO-216 (originally ETC-216).

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