The FOURIER trial to evaluate whether Evolocumab ( Repatha ) 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, non-fatal stroke, hospitalization for unstable angina or coronary revascularization ) and the key secondary composite endpoint ( cardiovascular death, non-fatal myocardial infarction or non-fatal stroke ).
No new safety issues were observed.
The EBBINGHAUS cognitive function trial conducted in FOURIER patients also achieved its primary endpoint, demonstrating that Evolocumab was non-inferior to placebo for the effect on cognitive function.
In the GLAGOV study, Evolocumab has produced an effect on atherosclerosis, the underlying cause of cardiovascular disease.
The FOURIER results have shown unequivocally the connection between lowering LDL cholesterol with Evolocumab and cardiovascular risk reduction, even in a population already treated with optimized statin therapy.
FOURIER ( Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk ) is a multinational phase 3 double-blind, randomized, placebo-controlled trial in approximately 27,500 patients who had either an myocardial infarction, an ischemic stroke or symptomatic peripheral artery disease and an LDL greater than or equal to 70 mg/dL or a non-HDL-C greater than or equal to 100 mg/dL on optimized statin therapy.
Optimized 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 randomized 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, myocardial infarction or stroke, whichever occured first.
EBBINGHAUS ( Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in high cardiovascUlar risk Subjects ) is a double-blind, placebo-controlled randomized 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.
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. ( Xagena )
Source: Amgen, 2017