HDL Mimetic May Not Benefit Patients With Familial Hypoalphalipoproteinemia

HDL Medical or clinical laboratory tests acronym or abbreviation of high density lipoprotein, type of blood cholesterol, also known as good cholesterol. Word HDL on ECG stripes lipid panel test result
Patients with very low levels HDL-cholesterol did not have improvements in carotid wall inflammation or dimensions when treated with an HDL mimetic.

Patients with very low levels of high-density lipoprotein (HDL) cholesterol due to genetic variants did not have improvements in carotid wall inflammation or dimensions when treated with HDL mimetic CER-001, according to study results published in Atherosclerosis.

In this multicenter, randomized, phase 3 clinical trial, 30 adult patients with loss-of-function variants in the ATP binding cassette subfamily (ABC)A1 or apolipoprotein (APO)A1 genes — familial hypoalphalipoproteinemia causing low levels of HDL-cholesterol (ie, £0.9 mmol/L) or apo A-I (ie, £1.1 g/L) — were recruited between 2015 and 2017 across 7 countries. All patients had a history of cardiovascular events and hypertriglyceridemia (ie, triglyceride levels >500 g/dL) or abnormal body mass index (ie, <17 kg/m2 or >40 kg/m2).

Participants were randomly assigned at a 2:1 ratio to receive CER-001 at 8 mg/kg or placebo weekly for 8 weeks, and then bi-monthly for 16 weeks. Participants could then enroll in an open-label 24-week bi-monthly extension program. Participants were assessed with physical examinations, laboratory analyses, electrocardiography, and magnetic resonance imaging.

Patients in this cohort had genetic variants in ABCA1 (n=15), APOA1 (n=13), or both genes (n=2). The mean HDL-cholesterol level was 0.35±0.25 mmol/L and mean apoA-I was 0.53±0.38 g/L. The treatment and placebo groups were well balanced for cardiovascular disease risk factors, and baseline HDL-cholesterol and apoA-I levels. However, 30% of the participants in the treatment group were diagnosed with subclinical atherosclerosis vs 70% in the placebo group.

At week 8, a significant upregulation of cholesterol efflux capacity was observed among participants in the treatment group, with an absolute treatment difference of 2.40% (95% CI, 1.04%-3.77%; P <.001). This difference was sustained through 24 weeks (2.53%; 95% CI, 1.19%-3.86%; P £.001) and 48 weeks (1.68%; 95% CI, 0.35%-3.01%; P =.0141).

The mean vessel wall area (MVWA) of the carotid artery did not change significantly from baseline (CER-001: 22.92±4.89 mm2 vs placebo: 27.13±11.28 mm2) to 8 weeks of treatment (treatment difference: 0.69 mm2; 95% CI, -0.54 to 1.93; P =.27). At week 48, no difference was observed (treatment difference: -0.20 mm2; 95% CI, -1.48 to 1.08; P =.76).

The change in carotid MVWA was not dependent on genetic variations (treatment difference, ABCA1: -0.84 mm2; 95% CI, -2.52 to 0.85; P =.32 vs APOA1: -0.59 mm2; 95% CI, -2.18 to 1.00; P =.45).

No alteration in the carotid arterial wall inflammation was observed between treatment and placebo groups (treatment difference, 0.10; 95% CI, -0.13 to -0.33; P =.37).

At 24 weeks, HDL-cholesterol, apoA-I, plasma lipid, and inflammatory biomarker levels were unaffected by treatment.

A major limitation of this study is the small sample size, which did not allow for individual analyses of the genetic subtypes.

“These results are in line with contemporary randomized clinical trials, which failed to demonstrate benefit of HDL infusion on imaging endpoints in atherosclerosis,” noted the study authors.


Zheng K H, Kaiser Y, van Olden C, et al. No benefit of HDL mimetic CER-001 on carotid atherosclerosis in patients with genetically determined very low HDL levels. Atherosclerosis. 2020;311:13-19. doi:10.1016/j.atherosclerosis.2020.08.004