Journal article
Pharmacodynamic relationship between PCSK9, alirocumab, and LDL-C lowering in the ODYSSEY CHOICE I trial
Journal of clinical lipidology, Vol.14(5), pp.707-719
09/2020
DOI: 10.1016/j.jacl.2020.07.009
PMID: 32928709
Abstract
The ODYSSEY CHOICE I study (NCT01926782) evaluated alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia receiving maximally tolerated statin or no statin.
The objective of the study was to assess the relationship between alirocumab, proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein cholesterol (LDL-C) concentrations with the CHOICE I alirocumab dosing regimen.
This analysis included 803 patients (547 statin-treated, 256 without statin) who were randomized to alirocumab 300 mg Q4W, alirocumab 75 mg every 2 weeks (Q2W), or placebo. 300 mg Q4W and 75 mg Q2W doses were adjusted to 150 mg Q2W at Week 12 if Week 8 LDL-C was >70 or >100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline.
Most patients remained on 300 mg Q4W without dose adjustment as they achieved study-defined LDL-C goals at Week 8 (statin-treated: 80.7%; no statin: 85.3%). LDL-C was reduced by 60.5%–71.9% over Weeks 20–24 in patients on 300 mg Q4W and 57.2%–63.0% in patients with dose adjustment from 300 mg Q4W to 150 mg Q2W. Statin-treated patients had higher cardiovascular risk as well as higher free PCSK9 and lower alirocumab concentrations (vs no statin), suggesting increased target-mediated clearance. Regardless of statin status, the most common adverse events in alirocumab-treated patients were injection-site reaction and headache.
Data provide further insight on alirocumab's mode of action in terms of relationship between alirocumab, PCSK9, and LDL-C, and disease severity, and support the use of alirocumab 300 mg Q4W as an efficacious dosing regimen for clinically meaningful LDL-C reductions.
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•Alirocumab, PCSK9, and LDL-C relationships were assessed with alirocumab 300 mg Q4W.•>80% of patients (including those on statins) achieved low-density lipoprotein cholesterol (LDL-C) goals with 300 mg Q4W.•Greater target-mediated clearance of alirocumab suggested in statin-treated patients.•Change to 150 mg Q2W more likely in statin-treated or higher baseline LDL-C patients.•Results provide further insight on alirocumab's mode of action.
Details
- Title: Subtitle
- Pharmacodynamic relationship between PCSK9, alirocumab, and LDL-C lowering in the ODYSSEY CHOICE I trial
- Creators
- Eli M. Roth - Sterling Research GroupJohn J.P. Kastelein - Amsterdam UMC Location University of AmsterdamChristopher P. Cannon - Baim Institute for Clinical ResearchMichel Farnier - Lipid Clinic, Point Médical and Department of Cardiology, CHU Dijon-Bourgogne, Dijon, FranceJames M. McKenney - Virginia Commonwealth UniversityA. Thomas DiCioccio - Regeneron (United States)Aurélie Brunet - Sanofi (France)Garen Manvelian - Regeneron (United States)William J. Sasiela - Regeneron (United States)Marie T. Baccara-Dinet - Sanofi (France)Jian Zhao - Regeneron (United States)Jennifer G. Robinson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of clinical lipidology, Vol.14(5), pp.707-719
- DOI
- 10.1016/j.jacl.2020.07.009
- PMID
- 32928709
- NLM abbreviation
- J Clin Lipidol
- ISSN
- 1933-2874
- eISSN
- 1876-4789
- Publisher
- Elsevier Inc
- Grant note
- Sanofi (https://doi.org/10.13039/100004339) Regeneron Pharmaceuticals, Inc (https://doi.org/10.13039/100009857)
- Language
- English
- Date published
- 09/2020
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984364422902771
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