Alirocumab treatment was found to be associated with clinically meaningful reductions in low-density lipoprotein cholesterol (LDL-C) levels in patients with homozygous familial hypercholesterolemia (HoFH), according to the results of the phase 3 randomized controlled ODYSSEY HoFH trial published in Journal of the American College of Cardiology.

A total of 69 patients with HoFH were randomly assigned 2:1 to receive alirocumab (150 mg; n=45) or placebo (n=24) subcutaneously every 2 weeks. After 12 weeks, all patients entered a 12-week open-label treatment period and received alirocumab every 2 weeks.

The trial’s primary endpoint of interest was the percent change in LDL-C compared with placebo from baseline to 12 weeks. Secondary endpoints included the percent change in apolipoprotein B, high-density lipoprotein-cholesterol (HDL-C), non-HDL-C, total cholesterol, lipoprotein(a), triglycerides, and apolipoprotein A1 at week 12 compared with baseline.

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The mean baseline LDL-C levels were 295.0 mg/dL in the alirocumab group and 259.6 mg/dL. In the placebo group. Almost all patients (97.1%) were on background statin therapy.

At week 12, the least squares mean difference in LDL-C from baseline was -26.9% in the alirocumab group and 8.6% in the placebo group (between-group difference, -35.6%; P <.0001). The percentage of patients who achieved ≥15% reduction in LDL-C levels was 61.9% in the alirocumab group and 12.5% in the placebo group (P =.0004). No patients in the placebo group achieved ≥50% reduction in LDL-C, compared with 26.7% in the alirocumab group (P =.0017).

The reduction from baseline to 12 weeks with alirocumab vs placebo was significant for apolipoprotein B (-29.8%), non-HDL-C (-32.9%), total cholesterol (-26.5%), and lipoprotein(a) levels (-28.4%; P <.0001 for all).

Lipid-lowering activity was maintained over the 12-week open-label period and similar effects were observed for patients who switched from placebo to alirocumab.

No treatment-emergent serious adverse events were reported in either group during the double-blind period. During the open-label period, 2 patients who had previously received alirocumab during the double-blind period discontinued treatment due to treatment-emergent adverse events (abnormal hepatic function and injection-site hypersensitivity).

The investigators noted that the relatively short duration of the trial and the exclusion of patients <18 years represent a limitation of the study.

“Treatment with alirocumab resulted in significant and clinically meaningful reductions in LDL-C in patients with HoFH, as well as significant reductions in other lipoprotein and lipid parameters,” the study authors concluded.

Disclosures: Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Blom DJ, Harada-Shiba M, Rubba P, et al. Efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia: The ODYSSEY HoFH trial. J Am Coll Cardiol. 2020;76(2):131-142. doi:10.1016/j.jacc.2020.05.027