PCSK9 antibody helps high-risk individuals to achieve NCEP-ATP III LDL-c target
AMG 145, A Monoclonal Antibody Against PCSK9, Facilitates Achievement of NCEP-ATP III LDL-C Goals Among High Risk Patients: An Analysis From the LAPLACE-TIMI 57 Trial.
Desai NR, Giugliano RP, Zhou J, et al.
J Am Coll Cardiol. 2013 Oct 11. doi: 10.1016/j.jacc.2013.09.048. [Epub ahead of print]
BackgroundThe National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommended LDL-c levels below 100 mg/dL in patients with established cardiovascular disease (CVD) or CVD equivalents. The 2004 updated guidelines with an optional target of <70 mg/dL  are not often achieved by patients at high risk for CV events, despite high potency statin treatment [2,3].
AMG 145 is a fully human, monoclonal, IgG2 antibody against proprotein convertase subtilisin
kexin type 9 (PCSK9), that yielded significant, dose-dependent reductions in LDL-c of up to 66% in the double blind, placebo-controlled LAPLACE-TIMI 57 trial . This analysis evaluated the ability of AMG 145 to enable subjects at high risk for adverse CV events in LAPLACE-TIMI 57 to achieve NCEP-ATP III LDL-c and other lipid goals.
- AMG 145 reduced LDL-C at 12 weeks as compared to baseline and as compared to placebo, by up to 64% for AMG 145 treatment every two weeks and up to 45% for treatment every 4 weeks.
- As compared to placebo, each dose of AMG 145 significantly increased the proportion of patients who achieved the NCEP-ATP III LDL-c target of <70 mg/dL at week 12, to 90% and 70% of subjects who received the top dose every 2 and 4 weeks respectively.
- LDL-c was sampled every 2 weeks, also in patients receiving AMG 145 once every 4 weeks. Up to 97% of these patients met the NCEP-ATP III LDL-c target at week 10. Up to 90% of patients receiving biweekly AMG 145 attained the NCEP-ATP III recommended LDL-c levels.
- All AMG 145 dose regimens were more likely than placebo to achieve non-HDL-c < 100 mg/dL or ApoB < 80 mg/dL or to achieve all three lipid targets.
- There were no significant differences in the rate of adverse events, including serious adverse events and elevations of creatine kinase and liver enzymes.
ConclusionThis analysis of the LAPLACE-TIMI 57 trial of subjects with established CVD shows that the addition of AMG 145 to background lipid-lowering therapy increases the potential of high risk individuals to achieve NCEP-ATP III LDL-c and other lipid parameter targets. Treatment with the highest tested dose once every two or once every four weeks allows almost all high-risk individuals to reach lipid targets. AMG 145 was well tolerated over 12 weeks.
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4. Giugliano RP, Desai NR, Kohli P et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebocontrolled, dose-ranging, phase 2 study. Lancet 2012;380:2007-17.
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