Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study.
The PCSK9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low-density lipoprotein-cholesterol (LDL-C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin-associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone.



Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL-C target levels were not met. The primary efficacy endpoint was LDL-C percentage change from baseline to W24. Mean baseline LDL-C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least-squares mean LDL-C changes from baseline to W24 were -51.7% and -53.5%, respectively (placebo [+4.7%]; both groups P<0.0001 versus placebo). In total, 63.9% and 70.3% of alirocumab-treated patients achieved their LDL-C targets at W24. Treatment-emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection-site reactions among the most common treatment-emergent adverse events.



Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL-C.



URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023879.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands e.s.stroes@amc.uva.nl.
Erik
E
Stroes
Duke University Medical Center, Durham, NC.
John R
JR
Guyton
Westside Medical Associates of Los Angeles Cedars-Sinai Heart Institute, Beverly Hills, CA.
Norman
N
Lepor
Lipid Unit, Hospital Universitario Miguel Servet, IIS Aragon, Zaragoza, Spain.
Fernando
F
Civeira
ECOGENE-21 Clinical and Translational Research Center and Department of Medicine, Université de Montréal, Chicoutimi, Quebec, Canada.
Daniel
D
Gaudet
Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Gerald F
GF
Watts
Sanofi, Clinical Development, R&D, Montpellier, France.
Marie T
MT
Baccara-Dinet
Sanofi, Chilly-Mazarin, France.
Guillaume
G
Lecorps
Regeneron Pharmaceuticals Inc, Tarrytown, NY.
Garen
G
Manvelian
Lipid Clinic, Point Médical, Dijon, France.
Michel
M
Farnier
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D003131:Combined Modality Therapy; D004035:Diet Therapy; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000628:therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D000075662:Injection Site Reaction / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D016896:Treatment Outcome; D000071449:Proprotein Convertase 9
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000069438:Ezetimibe; D011345:Fenofibrate; D000960:Hypolipidemic Agents; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
alirocumab; cardiovascular risk; low‐density lipoprotein cholesterol; placebo‐controlled; proprotein convertase subtilisin/kexin type 9