Abstract 16865: Safety and Tolerability of Very Low LDL-C Levels in Patients Treated with 52 Weeks of Evolocumab (AMG 145)
Introduction: Evolocumab (AMG 145), a fully human monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9), can reduce LDL-C to very low levels, particularly when administered with statins. We analyzed data from two recent 52-week studies of monthly evolocumab to assess the safety and tolerability of lowering LDL-C to<40 mg/dL.
Methods: We compared adverse events and lab abnormality rates in 1012 patients who ever achieved LDL-C <40 mg/dL (1005 [99.3%] treated with evolocumab) with 1187 patients who never achieved LDL-C <40 mg/dL (462 [38.9%] of whom were treated with evolocumab) in the DESCARTES and OSLER-1 studies. DESCARTES patients received background lipid regulating therapy based on NCEP risk and were then randomized 2:1 to blinded evolocumab 420 mg monthly or placebo. OSLER-1 randomized patients completing Phase 2 evolocumab studies to either standard of care (SoC) plus open-label evolocumab 420 mg administered monthly or SoC (followed-up quarterly) (2:1). Both studies evaluated patients over 52 weeks.
Results: Overall, patients who achieved very low (<40 mg/dL) as compared to higher (≥40 mg/dL) LDL-C levels had comparable rates of at least one AE: 77.8% vs 78.2% (Table). The occurrence of common AEs was balanced between very low and higher LDL-C groups. Analysis of laboratory abnormalities showed a higher rate of isolated elevated total bilirubin above 2x normal (0.9% vs 0.2%) in the very low vs higher LDL-C group, but less frequent elevation of transaminases above 3x normal in very low vs higher LDL-C treated patients (0.8% vs 1.9%). The overall event rates did not appear to be influenced by the use of intensive background statin therapy.
Conclusion: In two recent 52-week trials with evolocumab, patients who achieved very low LDL-C levels (<40 mg/dL) demonstrated comparable safety and tolerability vs patients with higher LDL-C levels (≥40 mg/dL) over one year of treatment.
Author Disclosures: M.J. Koren: Research Grant; Significant; Regeneron, Sanofi, Amgen, Pfizer. Consultant/Advisory Board; Modest; Regeneron, Sanofi. D. Blom: Honoraria; Modest; Amgen, Sanofi Aventis, AstraZeneca, MSD, PharmaDynamics, Aegerion. Consultant/Advisory Board; Modest; MSD, SanofiAventis, Aegerion. 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. E. Stroes: Employment; Modest; Academic Medical Center. Consultant/Advisory Board; Modest; Amgen, Sanofi, Novartis, Merck, Santaris, ISIS Pharmaceuticals. R. Somaratne: Employment; Significant; Amgen, Inc. A. Lowy: Employment; Significant; Amgen, Inc. M.L. Monsalvo: Employment; Significant; Amgen, Inc. H. Hsu: Employment; Significant; Amgen, Inc. S.M. Wasserman: Employment; Significant; Amgen, Inc. R. Scott: Employment; Significant; Amgen, Inc. M. Sabatine: Research Grant; Significant; Brigham and Women’s Hospital from Amgen, AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Bristol-Myers Squibb / Sanofi-aventis Joint Venture, Daiichi-Sankyo, Eisai, Genzyme, GlaxoSmithKline, Merck, Sanofi-aventis, Takeda, Abbott Laboratories, Accumetrics, Critical Diagnostics, Nonsphere, Roche Diagnostics. Consultant/Advisory Board; Modest; Aegerion, Amgen, Diasorin, GlaxoSmithKline, Merck, Pfizer, Sanofi-aventis, AstraZeneca, Vertex.
- © 2014 by American Heart Association, Inc.