Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher.
OBJECTIVE
Even with statins and other lipid-lowering therapy (LLT), many patients with heterozygous familial hypercholesterolemia (heFH) continue to have elevated low-density lipoprotein cholesterol (LDL-C) levels. ODYSSEY HIGH FH (NCT01617655) assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 monoclonal antibody, versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT.


METHODS
Patients were randomized to subcutaneous alirocumab 150 mg or placebo every 2 weeks (Q2W) for 78 weeks. The primary endpoint was percent change in LDL-C from baseline to week 24.


RESULTS
Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab (n = 71) and 201.0 mg/dl in the placebo groups (n = 35). Significant mean (standard error [SE]) reductions in LDL-C from baseline to week 24 were observed with alirocumab (-45.7 [3.5] %) versus placebo (-6.6 [4.9] %), a difference of -39.1 (6.0) % (P < 0.0001). Absolute mean (SE) LDL-C levels were reduced from baseline by 90.8 (6.7) mg/dl with alirocumab at week 24, with reductions maintained to week 78. Treatment-emergent adverse events were generally comparable between groups. Injection-site reactions were more frequent in the alirocumab group (8.3 %) versus placebo (5.7 %); most were mild in severity and did not result in study medication discontinuation.


CONCLUSIONS
In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT, alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals. Alirocumab was generally well tolerated.
Columbia University College of Physicians and Surgeons, Irving Institute for Clinical and Translational Research, Columbia University, 622 West 168th Street, New York, NY, 10032, USA. hng1@cumc.columbia.edu.
Henry N
HN
Ginsberg
Departments of Medicine and Genetics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
Daniel J
DJ
Rader
Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Frederick J
FJ
Raal
Duke University Medical Center, Durham, NC, USA.
John R
JR
Guyton
Sanofi, Montpellier, France.
Marie T
MT
Baccara-Dinet
Sanofi, Paris, France.
Christelle
C
Lorenzato
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Robert
R
Pordy
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Erik
E
Stroes
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
Alirocumab; Cardiovascular disease prevention; Cholesterol-lowering drugs; Familial hypercholesterolemia; LDL-C; PCSK9