A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I

• Published in: Atherosclerosis Vol. 254; pp. 254 - 262
• Main Authors: Roth, Eli M., Moriarty, Patrick M., Bergeron, Jean, Langslet, Gisle, Manvelian, Garen, Zhao, Jian, Baccara-Dinet, Marie T., Rader, Daniel J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.11.2016
• Subjects: Aged; Alirocumab; Antibodies, Monoclonal - administration & dosage; Atorvastatin Calcium - administration & dosage; Cardiovascular; Cardiovascular Diseases - blood; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - pathology; Cardiovascular risk; Cholesterol, LDL - blood; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hypercholesterolemia - drug therapy; LDL-C; Male; Middle Aged; PCSK9; Phase III; Placebo-controlled; Proprotein Convertase 9 - metabolism; Randomized; Simvastatin - administration & dosage; Treatment Outcome; Phase III; Randomized; LDL-C; Placebo-controlled; Cardiovascular risk; PCSK9; Alirocumab
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2016.08.043

In previous phase III studies, the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks (Q2W). CHOICE I (NCT01926782) evaluated 300 mg every 4 weeks (Q4W) in patients on either maximally tolerated statin or no statin, both ± other lipid-lowering therapies. CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk. Patients were randomized to alirocumab 300 mg Q4W, 75 mg Q2W (calibrator arm), or placebo for 48 weeks, with dose adjustment for either alirocumab arm to 150 mg Q2W at Week (W) 12 if at W8 LDL-C levels were >70/100 mg/dL (1.8/2.6 mmol/L) depending on cardiovascular risk or LDL-C reduction was <30% from baseline. Co-primary endpoints were percent LDL-C change from baseline to W24, and to time-averaged LDL-C over W21–24. Approximately two-thirds of randomized patients were receiving statins. At W12, 14.7% (no statin) and 19.3% (statin) of patients receiving alirocumab 300 mg Q4W required dose adjustment. At W24, significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W: mean differences were −52.7% (no statin; placebo: –0.3%) and −58.8% (statin; placebo: –0.1%). Average LDL-C reductions from baseline to W21–24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving (−56.9% vs. –1.6%) and receiving statin (−65.8% vs. –0.8%). Treatment-emergent adverse event rates ranged from 61.1 to 75.0% (placebo) and 71.5 to 78.1% (alirocumab 300 mg Q4W). Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering. •Many high CV risk patients do not reach their LDL-C goal on current therapies.•ODYSSEY CHOICE I evaluated alirocumab 300 mg Q4W/up to 150 mg Q2W.•Alirocumab 300 mg Q4W/up to 150 mg Q2W reduced LDL-C levels in patients ± statin.•Treatment-emergent adverse events were generally similar across the study groups.•Alirocumab 300 mg Q4W allows a treat-to-target approach ± concomitant statin.