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Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.

Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies.

Author information

1
From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.). peter.toth@cghmc.com.
2
From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK (D.P.); and Amgen Inc, Thousand Oaks, CA (R.D., C.D., Y.W., M.G., M.U., R.S., S.M.W.).

Abstract

BACKGROUND:

Evolocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), markedly reduces low-density lipoprotein cholesterol across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group.

METHODS:

This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and, of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in 2 OLE trials. AEs were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs, laboratory assessments, and AEs of interest were evaluated.

RESULTS:

Overall AE rates were similar between evolocumab and control in the parent trials (51.1% versus 49.6%) and in year 1 of OLE trials (70.0% versus 66.0%), as were those for serious AEs. Elevations of serum transaminases, bilirubin, and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive AEs were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups versus 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing antievolocumab antibodies were detected.

CONCLUSIONS:

Overall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in OLE trials for 1 year supports a favorable benefit-risk profile for evolocumab.

KEYWORDS:

antibodies monoclonal; cholesterol, LDL; long-term adverse events; myalgia; proprotein convertase 9

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