The phase 3 GLAGOV ( GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound ) trial evaluating the effect of Evolocumab ( Repatha ) on coronary artery disease ( CAD ) met its primary and secondary endpoints.
The GLAGOV study is a large serial coronary intravascular imaging trial designed to test whether treatment with the proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) inhibitor Evolocumab modifies atherosclerotic plaque build-up in the coronary arteries of patients already treated with optimized statin therapy.
GLAGOV is a multicenter, double-blind, randomized, placebo-controlled trial designed to evaluate the effect of Evolocumab on the change in burden of coronary artery disease in 968 patients undergoing cardiac catheterization and on optimized background statin therapy.
Patients were randomized 1:1 into two treatment groups to either receive monthly Evolocumab 420 mg or placebo subcutaneous injections.
The primary endpoint was change in percent atheroma volume ( PAV ) from baseline to week 78 compared to placebo, as determined by intravascular ultrasound ( IVUS ).
IVUS is a high-resolution imaging tool that allows for the quantification of coronary atheroma in the coronary arteries.
Secondary endpoints included PAV regression ( any reduction from baseline ); change in total atheroma volume ( TAV ) from baseline to week 78; and regression ( any reduction from baseline ) in TAV.
No new safety concerns were identified in the GLAGOV trial. The incidence of treatment-emergent adverse events was comparable among both groups.
Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ). It 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.
Cardiovascular disease is the leading cause of death worldwide. In the U.S., there are approximately 11 million people with atherosclerotic cardiovascular disease ( ASCVD ) and/or familial hypercholesterolemia ( FH ) who have uncontrolled levels of low-density lipoprotein ( LDL-C ) over 70 mg/dL, despite treatment with statins or other cholesterol-lowering therapies.
More than 60% of high-risk patients in Europe are still unable to adequately lower their LDL-C levels with statins or other currently approved lipid-lowering agents. Among very high-risk patients, the percentage is increased to more than 80%. It is estimated that less than 1% of people with FH ( heterozygous and homozygous forms ) in most countries are diagnosed. ( Xagena )
Source: Amgen, 2016