PCSK9 inhibitor non-inferior to placebo for effect on cognitive function
Amgen yesterday announced that the EBBINGHAUS cognitive function trial conducted in FOURIER patients achieved its primary endpoint, demonstrating that evolocumab was non-inferior to placebo for the effect on cognitive function.
SImultaneously, it was announced that the FOURIER evaluating whether evolocumab reduces the risk of cardiovascular events in patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) met its primary composite endpoint (cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalisation for unstable angina or coronary revascularisation) and the key secondary composite endpoint (cardiovascular death, non-fatal MI or non-fatal stroke).
Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
Evolocumab is approved in more than 40 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.
EBBINGHAUS (Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in high cardiovascUlar risk Subjects) is a double-blind, placebo-controlled randomised non-inferiority trial involving approximately 1,900 patients enrolled in the FOURIER outcomes study. Executive function (Spatial Working Memory strategy index – primary endpoint) and secondary endpoints of working memory, memory function, and psychomotor speed were assessed using a tablet-based tool (CANTAB) at baseline and select time points.
FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) is a multinational Phase 3 double-blind, randomised, placebo-controlled trial in approximately 27,500 patients who had either an MI, an ischemic stroke or symptomatic peripheral artery disease and an LDL ≥70 mg/dL or a non-HDL-C ≥100 mg/dL on optimised statin therapy. Optimised statin therapy was defined as at least atorvastatin 20 mg or equivalent daily with a recommendation for at least atorvastatin 40 mg or equivalent daily where approved. Patients were randomised to receive evolocumab subcutaneous 140 mg every two weeks or 420 mg monthly or placebo subcutaneous every two weeks or monthly. The study continued until at least 1,630 patients experienced a key secondary MACE (major adverse cardiac event) endpoint of cardiovascular death, MI or stroke, whichever occurred first.
Detailed results from the evolocumab FOURIER outcomes trial will be presented at the American College of Cardiology (ACC) 66th Annual Scientific Session Late-Breaking Clinical Trials session in Washington, D.C. on Friday, March 17 at 8 a.m. ET. Detailed results from the evolocumab EBBINGHAUS cognitive function trial will be presented at the Late-Breaking Clinical Trials session on Saturday, March 18 at 8 a.m. ET.