Approximately 10-20% of patients are unable to tolerate statins or the higher doses needed to achieve LDL cholesterol goals. Perprotein convertase subtilisin\/kexin type 9 (PCSK9) mediates the binding and trafficking of LDL receptors, and in phase 1 studies a human monoclonal antibody to to PCSK9 (AMG145)lowered LDL levels. The Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects (GAUSS) trial aimed to assess the efficacy and safety of AMG145 in patients with a documented history of muscle-related adverse effects with statins.<\/p>\n
In this 12-week, randomized, double-blind, placebo and ezetimibe-controlled study, 160 patients from 33 international sites were randomised equally to 1 of 5 groups: AMG145 alone at doses of 280 mg, 350 mg, or 420 mg; AMG145 at 420 mg plus 10 mg of ezetimibe; or 10 mg of ezetimibe plus placebo. AMG145 or placebo was administered subcutaneously every 4 weeks. All patients had intolerance to one or more statins because of muscle-related events. The primary endpoint was the percentage change from baseline to week 12 in ultracentrifugation-measured LDL cholesterol.<\/p>\n
After 12 weeks of treatment, mean changes in LDL cholesterol levels were \u221267 mg\/dL (\u221241%) for the AMG145, 280-mg, group; \u221270 mg\/dL (\u221243%) for the 350-mg group; \u221291 mg\/dL (\u221251%) for the 420-mg group; and \u2212110 mg\/dL (\u221263%) for the AMG145 420-mg\/ezetimibe group compared with \u221214 mg\/dL (\u221215%) for the placebo\/ezetimibe group (P < .001). Myalgia was the most common adverse event related to treatment seen during the study, occurring in 5 patients (15.6%) in the 280-mg group (n = 32); 1 patient (3.2%) in the 350-mg group (n = 31), 1 patient (3.1%) in the 420-mg group (n = 32), 6 patients (20.0%) receiving 420-mg AMG145\/ ezetimibe, and 1 patient (3.1%) receiving placebo\/ezetimibe.<\/p>\n