Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24 week, double-blind, randomized Phase 3 trial

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Abstract

Background

Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.

Methods

In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events ≥ 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.

Results

Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001). At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients, respectively).

Conclusions

Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.

Abbreviations

AE
adverse event
Apo
apolipoprotein
BMI
body mass index
CV
cardiovascular
CVD
cardiovascular disease
EOT
end of treatment
EZE
ezetimibe
HbA1c
glycated hemoglobin A1c
HDL-C
high-density lipoprotein cholesterol
IQR
interquartile range
ITT
intent-to-treat
LDL-C
low-density lipoprotein cholesterol
LDLR
low-density lipoprotein receptors
LLN
lower limit of normal
Lp(a)
lipoprotein (a)
LS
least squares
mITT
modified intent-to-treat
NCEP-ATPIII
National Cholesterol Education Program Adult Treatment Panel III
NEC
not elsewhere classified
Non-HDL-C
non-high-density lipoprotein cholesterol
PCSK9
proprotein convertase subtilisin/kexin 9
Q2W
every 2 weeks
R
randomization
SAEs
serious adverse events
SC
subcutaneously
SCORE
systematic coronary risk estimation
SD
standard deviation
SE
standard error
TEAEs
treatment-emergent adverse events
TGs
triglycerides
ULN
upper limit of normal

Keywords

PCSK9
Monoclonal antibodies
Cholesterol-lowering drugs
Hypercholesterolemia
LDL-C
Alirocumab

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