Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial

Dirk J. Blom, Mariko Harada-Shiba, Paolo Rubba, Daniel Gaudet, John J.P. Kastelein, Min Ji Charng, Robert Pordy, Stephen Donahue, Shazia Ali, Yuping Dong, Nagwa Khilla, Poulabi Banerjee, Marie Baccara-Dinet, Robert S. Rosenson

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103 Scopus citations


Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated low-density lipoprotein–cholesterol (LDL-C) levels and early onset atherosclerotic cardiovascular disease despite treatment with conventional lipid-lowering treatment. Objectives: This study was designed to assess LDL-C reduction with the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in adult patients with HoFH. Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase 3 study evaluated efficacy and safety of alirocumab 150 mg every 2 weeks. The primary endpoint was percent reduction from baseline in LDL-C versus placebo after 12 weeks of treatment. Results: Patients (N = 69) were randomized 2:1 to alirocumab or placebo. At baseline, background lipid-lowering treatment included 67 patients receiving statin (59 patients on high-intensity statin); 50 patients on ezetimibe; 10 patients on lomitapide; and 10 patients undergoing apheresis. Mean baseline LDL-C was 259.6 mg/dl in the placebo group and 295.0 mg/dl in the alirocumab group. At week 12, the least squares mean difference in LDL-C percent change from baseline was −35.6% (alirocumab [−26.9%] vs. placebo [8.6%]; p < 0.0001). Reductions (least squares mean difference) in other atherogenic lipids at week 12 were: apolipoprotein B, −29.8%; non–high-density lipoprotein cholesterol, −32.9%; total cholesterol, −26.5%; and lipoprotein(a), −28.4% (all p < 0.0001). No serious adverse events, permanent treatment discontinuations, or deaths due to treatment-emergent adverse events were reported during the double-blind treatment period. Conclusions: In the largest randomized controlled interventional trial in HoFH patients to date, alirocumab resulted in significant and clinically meaningful reductions in LDL-C at week 12. Alirocumab was generally well tolerated, with a safety profile comparable to that of placebo. (Study in Participants With Homozygous Familial Hypercholesterolemia [HoFH] [ODYSSEY HoFH] NCT03156621.)

Original languageEnglish
Pages (from-to)131-142
Number of pages12
JournalJournal of the American College of Cardiology
Issue number2
StatePublished - 14 Jul 2020


  • homozygous familial hypercholesterolemia
  • lipoprotein(a)
  • low-density lipoprotein
  • proprotein convertase subtilisin/kexin type 9 inhibitor


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