Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies

Abstract

Background: Evolocumab significantly lowers low-density lipoprotein cholesterol (LDL-C) when dosed 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) subcutaneously.

Hypothesis: LDL-C changes are comparable among different patient subgroups in a pooled analysis of data from phase 3 trials.

Methods: A total of 3146 patients received ≥1 dose of evolocumab or control in four 12-week phase 3 studies. Percent change from baseline in LDL-C for evolocumab 140 mg Q2W or 420 mg QM vs control was reported as the average of week 10 and 12 values. Quantitative and qualitative interactions between treatment group and subgroup by dose regimen were tested.

Results: In the pooled analysis, treatment differences vs placebo or ezetimibe were similar for both 140 mg Q2W and 420 mg QM doses across ages (<65 years, ≥65 years); gender; race (Asian, black, white, other); ethnicity (Hispanic, non-Hispanic); region (Europe, North America, Asia Pacific); glucose tolerance status (type 2 diabetes mellitus, metabolic syndrome, neither); National Cholesterol Education Program risk categories (high, moderately high, moderate, low); and European Society of Cardiology/European Atherosclerosis Society risk categories (very high, high, moderate, or low). Certain low-magnitude variations in LDL-C lowering among subgroups led to significant quantitative interaction P values that, when tested by qualitative interaction, were not significant. The incidences of adverse events were similar across groups treated with each evolocumab dosing regimen or control.

Conclusions: Consistent reductions in LDL-C were observed in the evolocumab group regardless of demographic and disease characteristics.

Keywords: age; cardiovascular disease; diabetes; dose; gender; race.

Conflict of interest statement

Dr. Stroes reports that his institution has received lecturing fees/grants from Amgen Inc., Merck, Novartis, Regeneron Pharmaceuticals, and Sanofi.

Dr. Robinson reports consulting fees from Amgen Inc., Eli Lilly, Merck, Pfizer, Regeneron Pharmaceuticals, and Sanofi, and reports that her institution has received grants from Acasti Pharma, Amarin Corporation, Amgen Inc., AstraZeneca, Eisai, Esperion, Merck, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Takeda Pharmaceutical Company Ltd.

Dr. Raal reports consulting fees from Amgen Inc. and Sanofi related to PCSK9 inhibitors, and institutional research funding related to PCSK9 inhibitor clinical trials from Amgen Inc. and Sanofi.

Dr. Dufour reports consulting fees from Amgen Inc., Regeneron Pharmaceuticals/Sanofi, Aegerion Pharmaceuticals, and Janssen Pharmaceuticals, research funding from Amgen Inc. and lecturing fees form Amgen Inc., Valeant Pharmaceuticals International and Sanofi.

Dr. Sullivan reports advisory committee/lecture fees from Abbott, Amgen Inc., AstraZeneca, Mylan, and Pfizer; and that he has received grants from Abbott, Amgen Inc., Mylan, Sanofi, and Novartis.

Drs. Kassahun and Wasserman are employees of and stockholders in Amgen Inc. Dr. Wasserman appears on a number of pending patents owned by Amgen Inc. relating to evolocumab and PCSK9 inhibition. Dr. Ma is employed on behalf of Amgen Inc.

Dr. Koren is employed by a company that has received research grants and consulting fees from Amgen Inc. and other companies developing therapies for hyperlipidemia.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1

Percent change from baseline in LDL‐C by scheduled visit and treatment group. Abbreviations: LDL‐C, low‐density lipoprotein cholesterol; PO, orally; QD, daily; QM, monthly; Q2W, every 2 weeks; SC, subcutaneously; SE, standard error

Figure 2

Waterfall plots showing percent change from baseline in LDL‐C at the mean of weeks 10 and 12 in patients who did (A) and did not (B) receive combination statin therapy. Plot is based on observed data; no imputation is used for missing values. *patients with early termination. Abbreviations: LDL‐C, low‐density lipoprotein cholesterol; n, number of patients randomized, dosed and who were evaluable for LDL‐C at the timepoint; QM, monthly; Q2W, every 2 weeks

Figure 3

Percent change from baseline in LDL‐C at mean of weeks 10 and 12 for evolocumab vs placebo or ezetimibe according to individual study (A), race (B), patient demographic characteristics (C), and disease status (D). Abbreviations: EAS, European atherosclerosis society; ESC, European Society of Cardiology; LDL‐C, low‐density lipoprotein cholesterol; NA, not applicable; NCEP, National Cholesterol Education Program; n1, number of patients in the subgroup of interest included in the repeated measures model receiving evolocumab; n2, number of patients in the subgroup of interest included in the repeated measures model receiving placebo; QD, daily; QM, monthly; Q2W, every 2 weeks