Abstract
Abstract 16611: Pharmacodynamic Relationship Between PCSK9, Alirocumab, and LDL-C Lowering in the ODYSSEY CHOICE I Trial
Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A16611-A16611
11/11/2016
Abstract
AimODYSSEY CHOICE I (NCT01926782) evaluated 300 mg alirocumab (ALI) every 4 weeks (Q4W) for 48 weeks in patients with hypercholesterolemia at moderate to very-high cardiovascular (CV) risk either on maximally tolerated statin or no statin and/or other lipid-lowering therapies. Described here, are the relationships between PCSK9 levels, ALI levels, and reduction in LDL-C over the first 24 weeks in statin-treated patients only.MethodsThe statin-treated pharmacodynamics (PD) population consisted of 299 patients. Dose adjustment to 150 mg every two weeks (Q2W) occurred at Week (W)12 if LDL-C levels at W8 were >70 or >100 mg/dL depending on CV risk, or if LDL-C reduction was <30% from baseline. LDL-C was calculated using the Friedewald formula. Concentrations of ALI and total/free PCSK9 were determined by ELISA up to W24.ResultsALI 300 mg Q4W substantially reduced circulating free PCSK9 concentration at W4, resulting in substantial LDL-C reductions, which were maintained for the duration of the trial. Four of five patients (80.7%) did not require dose adjustment. Patients who required dose adjustment (19.3%) showed higher LDL-C at baseline, higher variability in LDL-C levels from ALI peak (2 weeks’ post-dose) to ALI trough concentrations (4 weeks’ post-dose), and higher free PCSK9 and lower ALI trough concentrations at W12 versus patients not requiring dose adjustment (Figure). At W20-24, both patient groups showed similar free PCSK9 concentrations and LDL-C reductions; the monthly exposure (AUC) of ALI 300 mg Q4W was similar to the monthly exposure of 150 mg Q2W. The most common adverse events occurring in patients on statin were injection site reaction, nasopharyngitis and upper respiratory tract infection.ConclusionsThis PD analysis of CHOICE I supports the use of ALI 300 mg Q4W as an alternative starting dose for patients who prefer an Q4W dosing regimen and demonstrates the value of the LDL-C-based dosing interval adjustment.
Details
- Title: Subtitle
- Abstract 16611: Pharmacodynamic Relationship Between PCSK9, Alirocumab, and LDL-C Lowering in the ODYSSEY CHOICE I Trial
- Creators
- Eli Roth - 1Med Director, Sterling Rsch Group, Cincinnati, OH 2Vascular Medicine, Academic Med Cntr, Univ of Amsterdam, Amsterdam, Netherlands 3None, Harvard Clinical Rsch Institute, Boston, MA 4Lipid Clinic, Point Med, Dijon, France 5None, National Clinical Rsch, Inc, Richmond, VA 6Pharmacometrics, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 7DSAR, Sanofi, Montpellier, France 8Clinical Sciences, Cardiovascular and Metabolism Therapeutics, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 9None, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10R&D, Sanofi, Montpellier, France 11Biostatistics, Sanofi, Chilly Mazarin, France 12Depts of Epidemiology & Medicine, Univ of Iowa, Iowa City, IAJohn KasteleinChristopher CannonMichel FarnierJames McKenneyA DiCioccioAurelie BrunetGaren ManvelianWilliam SasielaMarie Baccara-DinetGuillaume LecorpsJennifer Robinson
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.134(Suppl_1 Suppl 1), pp.A16611-A16611
- Publisher
- by the American College of Cardiology Foundation and the American Heart Association, Inc
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/11/2016
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984364393302771
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