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The Lancet Publication Of LAPLACE-TIMI 57 And MENDEL Studies Showed AMG 145 Significantly Reduced LDL Cholesterol
AMG 145 is an investigational fully human monoclonal antibody directed against PCSK9, a protein that reduces the liver's ability to remove LDL-C, or "bad" cholesterol from the blood. LDL-C is a major contributor of risk for cardiovascular disease.[i] Despite the availability of various treatments for lowering LDL-C, it is estimated that in two-thirds of treated high-risk patients, LDL-C is not well controlled.[ii], [iii]
LAPLACE-TIMI 57 Primary Results
- Results from the LAPLACE-TIMI 57 study showed that all six dose regimens of AMG 145 significantly decreased LDL-C, measured by preparative ultracentrifugation, from baseline compared to placebo at week 12 in patients at risk for cardiovascular disease already on statin therapy (p<0.0001).
- In these at risk patients, LAPLACE-TIMI 57 showed the addition of AMG 145 to statin therapy, with or without ezetimibe, achieved significant decreases in LDL-C.
- At week 12, AMG 145 reduced LDL-C, measured by preparative ultracentrifugation, by up to 66 percent when dosed every two weeks (Q2W) and up to 50 percent when dosed very four weeks (Q4W), compared to placebo (p<0.001 for the highest dose vs. placebo).
- The mean reduction in LDL-C versus placebo for AMG 145 dosed Q2W was 42 percent in the 70 mg group; 60 percent in the 105 mg group; and 66 percent in the 140 mg group.
- The mean reduction in LDL-C versus placebo for AMG 145 dosed Q4W was 42 percent in the 280 mg group; 50 percent in the 350 mg group; and 50 percent in the 420 mg group.
- The most commonly reported adverse events (AEs) for AMG 145 were nasopharyngitis, cough and nausea.
"Statins have been a critical tool in the management of high cholesterol, but even at high doses, statins do not always achieve the targeted level of LDL (bad) cholesterol in our high risk patients," said
Efficacy and Safety of a Fully Human Monoclonal Antibody Against PCSK9 as Monotherapy for Hypercholesterolemia: Results from the MENDEL Study, a Global Phase 2 Trial of AMG 145
- MENDEL is the first monotherapy study of a PCSK9-inhibitor, and evaluated AMG 145 in patients who were not taking a statin.
- Results of the study at week 12 demonstrated that AMG 145, dosed Q2W or Q4W, significantly reduced LDL-C, measured by preparative ultracentrifugation, compared to placebo (p<0.001).
- At week 12, treatment with AMG 145 reduced LDL-C, measured by preparative ultracentrifugation, by up to 47 percent in the groups dosed Q2W; and up to 53 percent from baseline in the groups dosed Q4W, compared to placebo (p<0.001 for the highest dose vs. placebo).
- The mean decrease in LDL-C from baseline for AMG 145 dosed Q2W was 41 percent in the 70 mg group; 44 percent in the 105 mg group; and 51 percent in the 140 mg group compared to four percent for placebo.
- The mean decrease in LDL-C from baseline for AMG 145 dosed Q4W was 39 percent in the 280 mg group; 43 percent in the 350 mg group; and 48 percent in the 420 mg group compared to five percent increase for placebo.
- The most commonly reported AEs for AMG 145, were upper respiratory tract infection, nasopharyngitis and diarrhea.
"In the MENDEL study, AMG 145 monotherapy showed robust reductions in serum LDL-C with both the Q2W and Q4W dosing regimens in patients with high cholesterol regardless of sex, age, race or cardiovascular risk factors," said
These studies are two of four Phase 2 studies of AMG 145 being presented at the American Heart Association Scientific Sessions 2012.
LAPLACE-TIMI 57 Study Design
LAPLACE-TIMI 57 (LDL-C Assessment with P
MENDEL Study Design
MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy For Easing Lipid Levels) is a Phase 2 randomized, multi-center, double-blind, controlled trial designed to evaluate the efficacy, safety and tolerability of AMG 145 in 406 patients with low cardiovascular risk (LDL-C > 100 mg/dL and < 190 mg/dL) who were not receiving statin therapy. AMG 145 was evaluated across nine treatment groups, including AMG 145 at 70 mg, 105 mg and 140 mg dosed Q2W compared to placebo Q2W; and AMG 145 at 280 mg, 350 mg and 420 mg dosed Q4W compared to placebo Q4W; or daily ezetimibe 10 mg. The primary endpoint was percentage change from baseline in LDL-C, measured by preparative ultracentrifugation, at week 12. Secondary efficacy endpoints included the absolute change from baseline in LDL-C at week 12 and the percentage changes from baseline at week 12 in non-high-density lipoprotein (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio and ApoB/ApoA1 ratio.
About AMG 145
AMG 145 is a fully human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that reduces the liver's ability to remove LDL-C from the blood and thereby causes bad cholesterol to increase. AMG 145, developed by
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[ii] AHA 2011 Update Online. http://circ.ahajournals.org/content/123/4/e18.full. Page 119. Accessed
[iii] Dyslipidaemia. The Lancet, 362 (9385): 717–31.doi:10.1016/S0140-6736(03)14234-1.