Disappointing Results for HDL-C Therapy

A synthetic version of “good” cholesterol or HDL-C did not reduce plaque as hoped when injected into the arteries of patients who had recently had a heart attack.

Reporting at the ACC Scientific Sessions, Stephen Nicholls, MBBS, PhD, director of research at the Vascular Research Centre at the South Australian Health and Medical Research Institute in Adelaide said the phase 2 CARAT trial failed to meet its primary endpoint.

Discussing the findings at a news conference this morning, 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 that had previously been shown to be at least 30% blocked, Nicholls said.

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

Researchers had hoped that by mimicking the body’s natural defenses in which HDL-C clears 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 LDL in patients with the genetic condition known as familial hypercholesterolemia.

In the CARAT trial, researchers enrolled 301 patients, average age 60 and 80% men, who had had a recent heart attack and had 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 it the reduction of these arterial deposits in the group that got the CER-100 and those who got a placebo.

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

At the news conference he said 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 US, Australia, Hungary, and the Netherlands. Patients with uncontrolled diabetes, extremely elevated triglycerides, heart failure, liver disease or kidney disease were excluded from the study.