title: Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials).
abstract: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, with limited treatment options. This analysis evaluated the effect of a monoclonal antibody to proprotein convertase subtilisin/kexin 9, alirocumab 150 mg every 2 weeks (Q2W), on Lp(a) levels in pooled data from 3 double-blind, randomized, placebo-controlled, phase 2 studies of 8 or 12 weeks' duration conducted in patients with hypercholesterolemia on background lipid-lowering therapy (NCT01266876, NCT01288469, and NCT01288443). Data were available for 102 of 108 patients who received alirocumab 150 mg Q2W and 74 of 77 patients who received placebo. Alirocumab resulted in a significant reduction in Lp(a) from baseline compared with placebo (-30.3% vs -0.3%, p <0.0001). Median percentage Lp(a) reductions in the alirocumab group were of a similar magnitude across a range of baseline Lp(a) levels, resulting in greater absolute reductions in Lp(a) in patients with higher baseline levels. Regression analysis indicated that <5% of the variance in the reduction of Lp(a) was explained by the effect of alirocumab on low-density lipoprotein cholesterol. In conclusion, pooled data from 3 phase 2 trials demonstrate substantive reduction in Lp(a) with alirocumab 150 mg Q2W, including patients with baseline Lp(a) >50 mg/dl. Reductions in Lp(a) only weakly correlated with the magnitude of low-density lipoprotein cholesterol lowering.
authors: Department of Medicine, Université de Montreal, The ECOGENE-21 Clinical Research Center and Lipid Clinic, Chicoutimi, Quebec, Canada. Electronic address: daniel.gaudet@umontreal.ca.
authors: Daniel
authors: D
authors: Gaudet
authors: The Christ Hospital Heart and Vascular Center/The Lindner Research Center, Cincinnati, Ohio.
authors: Dean J
authors: DJ
authors: Kereiakes
authors: Virginia Commonwealth University, Richmond, Virginia.
authors: James M
authors: JM
authors: McKenney
authors: Sterling Research Group, Cincinnati, Ohio.
authors: Eli M
authors: EM
authors: Roth
authors: Sanofi, Paris, France.
authors: Corinne
authors: C
authors: Hanotin
authors: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors: Daniel
authors: D
authors: Gipe
authors: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors: Yunling
authors: Y
authors: Du
authors: Sanofi, Paris, France.
authors: Anne-Catherine
authors: AC
authors: Ferrand
authors: Columbia University, New York, New York.
authors: Henry N
authors: HN
authors: Ginsberg
authors: Metabolic and Atherosclerotic Research Center, Cincinnati, Ohio.
authors: Evan A
authors: EA
authors: Stein
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000069059:Atorvastatin; D002793:Cholic Acids / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D011758:Pyrroles / Q000008:administration & dosage; D043202:Steroid Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy*; D020860:Subtilisin / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002793:Cholic Acids; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D011758:Pyrroles; D000069059:Atorvastatin; D020860:Subtilisin; C571059:alirocumab