BioCentury
ARTICLE | Clinical News

Evolocumab: Phase III data

December 23, 2013 8:00 AM UTC

Top-line data from the double-blind, 6-arm, international Phase III MENDEL-2 trial in 614 patients with high cholesterol (LDL-C levels of >=100 mg/dL and <190 mg/dL) who were not receiving lipid-lowering therapy showed that subcutaneous evolocumab given monthly at 420 mg and every 2 weeks at 140 mg each met the co-primary endpoints of a greater percent reduction in LDL-C from baseline to week 12 and a greater mean percent reduction in LDL-C from baseline to weeks 10 and 12 compared to both placebo and once-daily oral ezetimibe. To achieve statistical significance on each endpoint, Amgen said each evolocumab regimen had to achieve a p-value of <0.025 compared to both placebo and ezetimibe. The company said the mean percent reductions in LDL-C with evolocumab compared to placebo and ezetimibe were consistent with results observed in the Phase II MENDEL trial. The most common adverse events reported were headache, diarrhea, nausea and urinary tract infection. The trial enrolled patients with a 10-year Framingham risk score of <=10% to receive 1 of 2 regimens of evolocumab, ezetimibe or placebo.

In 2012, Amgen reported data from the Phase II MENDEL trial to treat hypercholesterolemia showing that 140 mg evolocumab given every 2 weeks led to a 50.9% mean reduction in LDL-C from baseline to week 12 vs. 3.7% for placebo (p<0.0001). Additionally, 420 mg evolocumab given every 4 weeks led to a 48% mean reduction in LDL-C from baseline to week 12 vs. a 4.5% increase for placebo (p<0.0001). Both evolocumab regimens also significantly reduced LDL-C vs. ezetimibe (14.7%; p<0.0001 for both) (see BioCentury, Nov. 12, 2012). ...