Evolocumab ( Repatha ) is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ).
PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL cholesterol ( LDL-C ), from the blood.
Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.

PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating Evolocumab in 22 clinical trials, with a combined planned enrollment of approximately 35,000 patients.

The phase 3 program includes 16 trials to evaluate Evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia ( LAPLACE-2 and YUKAWA-2 ); in patients with hyperlipidemia who cannot tolerate statins ( GAUSS-2 and GAUSS-3 ); as a stand-alone treatment in patients with hyperlipidemia ( MENDEL-2 ); in patients whose elevated cholesterol is caused by genetic disorders called heterozygous ( RUTHERFORD-2 and TAUSSIG ) and homozygous ( TESLA and TAUSSIG ) familial hypercholesterolemia; the effects of Evolocumab on lipoprotein metabolism ( FLOREY ); and the administration of Evolocumab in statin-treated hyperlipidemic patients ( THOMAS-1 and THOMAS-2 ).

Five ongoing studies in the Evolocumab phase 3 program will provide long-term safety and efficacy data. These include FOURIER ( Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk ), which will assess whether treatment with Evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 27,500 patients with cardiovascular disease; EBBINGHAUS ( Evaluating PCSK9 Binding AntiBody Influence oN CoGnitive HeAlth in High CardiovascUlar Risk Subjects ), which will evaluate the effect of Evolocumab on cognitive function in a subset of patients enrolled in FOURIER; OSLER-2 ( Open Label Study of Long TERm Evaluation Against LDL-C Trial-2 ) in patients with high cholesterol who completed any of the phase 3 studies; GLAGOV ( GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound ), which will determine the effect of Evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization; and TAUSSIG ( Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects with Genetic LDL Disorders ), which will assess the long-term safety and efficacy of Evolocumab on LDL cholesterol in patients with severe familial hypercholesterolemia including patients with homozygous familial hypercholesterolemia.
The DESCARTES ( Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study ) study, a long-term safety and efficacy trial in patients with hyperlipidemia at risk for cardiovascular disease, has been completed. ( Xagena )

Source: Amgen, 2015

XagenaMedicine2015