Abstract 16270: Evaluation of the Relationship Between Evolocumab 140 mg Every Two Weeks and 420 mg Monthly Dosing Regimens
Introduction: Understanding the pharmacodynamic profile of a therapeutic monoclonal antibody against PCSK9 is critical for selecting optimal dosing regimens. We assessed the effects of SC evolocumab 140 mg every 2 weeks (Q2W) and 420 mg monthly (QM) on LDL-C and other lipid parameters in hyperlipidemic patients.
Methods: Calculated LDL-C, lipid parameters, and unbound PCSK9 at pre-dose and every two weeks until week 12 were aggregated from 248 patients receiving evolocumab or placebo in the phase 2 MENDEL and LAPLACE-TIMI 57 studies. In addition, data were analyzed for 56 patients who participated in sub-studies at weeks 9 and 11 to determine the time-averaged effect (TAE) from the area under the curve.
Results: The temporal changes in calculated LDL-C for Q2W and QM dosing are shown (Figure). The greatest calculated LDL-C reductions were similar for Q2W (-72.1% 1 week after dosing) and QM (-69.0% 2 weeks after dosing) regimens; 95% mean difference CI (-11.3%, 5.0%). There was less attenuation in calculated LDL-C at the end of the dosing interval for Q2W (-64.1% 2 weeks after the dose) vs QM (-56.4% 4 weeks after the dose) regimens (95% mean difference CI -12.6%, -2.8%). Similar reductions in the mean of weeks 10 and 12 calculated LDL-C (95% CI) of -64.5% (-67.6, -61.4) and -63.5% (-66.6, -60.5) were observed with Q2W and QM dosing. In the sub-study, calculated LDL-C TAE (95% CI) of -68.3% (-73.5, -63.0) and -62.6% (-67.4, -57.8) were observed with Q2W and QM dosing, respectively; 95% mean difference CI (-12.6%, 1.3%). Changes in other lipid parameters and unbound PCSK9 showed no clinically significant differences between Q2W and QM dosing.
Conclusion: Evolocumab 140 mg biweekly and 420 mg monthly administration result in comparable changes in LDL-C and other lipid parameters over a month suggesting that these doses are clinically equivalent.
Author Disclosures: S.M. Wasserman: Employment; Significant; Amgen Employee. M. Koren: Research Grant; Modest; Amgen, Inc. R.P. Giugliano: Honoraria; Modest; Daiichi Sankyo, Merck. Consultant/Advisory Board; Modest; Amgen Inc., Daiichi Sankyo, Merck, Janssen. Research Grant; Significant; Amgen, Daiichi Sankyo, Merck. J.P. Gibbs: Employment; Significant; Amgen, Inc. J. Legg: Employment; Significant; Amgen, Inc. M.G. Emery: Employment; Significant; Amgen, Inc. P.C. Haughney: Employment; Significant; Amgen, Inc. T. Liu: Employment; Significant; Amgen, Inc. R. Scott: Employment; Significant; Amgen, Inc. M.S. Sabatine: Research Grant; Modest; Amgen, Inc., AstraZeneca/BMS Alliance, BMS/Sanofi Joint Venture, Daiichi-Sanyo, Eisai, Genzyme, GSK, Merck, Sanofi, Takeda, Abbott, Accumetrics, Critical Diagnostics, Nanosphere, Roche Diagnostics. Consultant/Advisory Board; Modest; Aegerion, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Intarcia, Merck, Pfizer, Sanofi-aventis, AstraZeneca, and Vertex.
- © 2014 by American Heart Association, Inc.