CARAT: Pre-beta HDL mimetic not beneficial for treatment of arterial plaque

WASHINGTON — Infusion of CER-001, a pre-beta HDL mimetic, did not have a significant effect in the treatment of coronary disease progression, according to the results of the CARAT study presented at the American College of Cardiology Scientific Session.

While epidemiological studies suggest that HDL can be effective in CVD prevention, HDL-raising agents are not proven to reduce CV events, Stephen J. Nicholls, MBBS, PhD, from South Australian Health and Medical Research Institute, Adelaide, Australia, said during a presentation.

Early studies of CER-001 (Cerenis Therapeutics) showed a possible benefit in patients with ACS or genetic dyslipidemia, he said.

Stephen J. Nicholls

“Early imaging studies demonstrated favorable effects of HDL infusions on coronary atherosclerosis,” Nicholls said. “This provided support for development of HDL-targeted agents as potential anti-atherosclerotic therapies.”

Researchers enrolled 301 patients with ACS and high plaque burden (mean age, 60 years; 80% men) from 33 global centers in a phase 2, double blind trial to assess the effect compared with placebo of 10 weekly infusions of CER-001 at a 3 mg/kg dose on coronary atherosclerosis.

All patients underwent IVUS imaging at baseline and at the end of the study.

The primary efficacy endpoint was the nominal change in percent atheroma volume from baseline to the conclusion of the study.

Median change in percent atheroma volume was –0.41% (95% CI, –1.6 to 0.8; P = .01) in the placebo group but only –0.09% (95% CI, –1.8 to 0.5; P = .67) in the CER-001 group (P for interaction = .15).

In addition, CER-001 was not better than placebo in median change in volume of the entire vessel length (placebo group, –6.6 mm³; 95% CI, –13.7 to 1.7; P < .001; CER-001 group, –5.6 mm³; 95% CI, –12.4 to 1.7; P < .001; P for interaction = .64) or median change in volume of the most diseased 10-mm segment (placebo group, –3 mm³; 95% CI, –6.9 to 1.5; P < .001; CER-001 group, –3.5 mm³; 95% CI, –7.7 to 1.8; P < .001; P for interaction = .51).

“This is another disappointing result for the low dose of this agent in a post-ACS setting,” Nicholls said in a press conference. “Whether this has a valuable effect in other clinical settings can only be determined by the clinical trials, but I think the HDL field continues to be an unfulfilled promise.” – by Dave Quaile

Reference:

Nicholls SJ, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 17-19, 2017; Washington, D.C.

Disclosure: The study was funded by Cerenis Therapeutics. Nicholls reports financial ties with AstraZeneca, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, InfraReDx, Kowa, LipoScience, Merck, Novartis, Resverlogix, Roche, Sanofi/Regeneron, Takeda and The Medicines Company.