Amgen announced that results from the LAPLACE-TIMI 57, MENDEL, and GAUSS Phase 2 studies evaluating AMG 145 in hypercholesterolemic patients with or without statins, respectively, showed that treatment with AMG 145 resulted in a statistically significant reduction in low-density lipoprotein (LDL) cholesterol. AMG 145 is a fully human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove LDL-C from the blood and thereby causes bad cholesterol to increase.
LAPLACE-TIMI 57 (LDL-C Assessment with P CSK9 monoclonaL Antibody inhibition Combined with statin thErapy – Thrombolysis In Myocardial Infarction-57) was a randomized, double-blind, dose-ranging, placebo-controlled study that included eight treatment arms to evaluate the efficacy, safety and tolerability of AMG 145, administered subcutaneously, in 629 patients at risk for cardiovascular disease with LDL-C >85 mg/dL when added to a stable dose of statin with or without ezetimibe (Zetia; Merck). At Week 12, AMG 145 reduced LDL-C by up to 66% when dosed every two weeks (Q2W) and up to 50% when dosed very four weeks (Q4W), compared to placebo (P<0.001 for the highest dose vs. placebo). The mean reduction in LDL-C vs. placebo for AMG 145 dosed Q2W was 42% in the 70mg group; 60% in the 105mg group; and 66% in the 140mg group. The mean reduction in LDL-C vs. placebo for AMG 145 dosed Q4W was 42% in the 280mg group; 50% in the 350mg group; and 50% in the 420mg group.
MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy For Easing Lipid Levels) was 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. MENDEL is the first monotherapy study of a PCSK9-inhibitor, and evaluated AMG 145 in patients who were not taking a statin. At Week 12, treatment with AMG 145 reduced LDL-C by up to 47% in the groups dosed Q2W; and up to 53% 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% in the 70mg group; 44% in the 105mg group; and 51% in the 140mg group compared to four percent for placebo. The mean decrease in LDL-C from baseline for AMG 145 dosed Q4W was 39% in the 280mg group; 43% in the 350mg group; and 48% in the 420mg group compared to a five percent increase for placebo.
GAUSS (Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin intolerant Subjects) was a 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study to assess the efficacy, safety and tolerability of AMG 145 in 160 patients ages 18–75 years who could not tolerate effective statin doses due to muscle-related side effects. At Week 12, the mean decrease from baseline in LDL-C, measured by preparative ultracentrifugation, was 41% in the AMG 145 280mg group; 43% in the AMG 145 350mg group; 51% in the AMG 145 420mg group; 63% in the AMG 145 420mg/ezetimibe 10mg group; and 15% in the placebo/ezetimibe 10mg group. The reduction in LDL-C with all doses of AMG 145 was significantly greater than that observed with ezetimibe alone (P<0.001).
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