Synthetic Cholesterol Drug Disappoints in Trial

A synthetic version of high-density lipoprotein (HDL), known as “good” cholesterol, did not reduce plaque as hoped when injected into the arteries of patients who recently had a heart attack.

Reporting at the 66th Scientific Session of the American College of Cardiology (ACC), Stephen Nicholls, MBBS, PhD, director of research at the Vascular Research Centre at the South Australian Health and Medical Research Institute, said the phase 2 CARAT trial failed to meet its primary endpoint.

Discussing the findings at a news conference this weekend, Nicholls said he has not given up on HDL research, but added, "I feel like I come here every 3 months with negative results—I feel like I need a hug."

The goal had been to change the volume of fatty deposits in a coronary artery previously shown to be at least 30% blocked, Nicholls said.

The product, called CER-001, is manufactured by Cerenis Therapeutics.

Researchers had hoped that mimicking the body’s natural defenses that HDL-C uses to clear LDL cholesterol from the arteries, they got reverse plaque in patients at risk of adverse cardiovascular events.

Studies have suggested that levels of HDL-C above 40 in men and above 50 in women may be protective.

The synthetic product might also reduce dangerously high low-density lipoprotein (LDL)—bad cholesterol—in patients with familial hypercholesterolemia. In the CARAT trial, researchers enrolled 301 patients with an average age of 60, of whom 80% were men. The enrollees had a recent heart attack and at least one coronary artery blocked by more than 30% with fatty deposits.

Participants got 10 weekly infusions of CER-100 or placebo.

At the end of the study, participants’ arteries were examined by ultrasound. The team also looked at plaque volume, cholesterol levels, and the safety and tolerability of CER-100.

But there was no significant difference in the reduction of these arterial deposits in the group administered CER-100 and those administered placebo.

“We are disappointed that low-dose CER-001 did not show a benefit,” Nicholls said.

At the news conference, he said "HDL is more complicated than LDL and we know very little about it," adding that several companies continue to research HDL therapies and that they should.

The study sites were in the United States, Australia, Hungary, and the Netherlands. Patients with uncontrolled diabetes, extremely elevated triglycerides, heart failure, liver disease or kidney disease were excluded from the study.