Drugs Xagena
Evolocumab 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-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.
The phase 3 program includes 13 trials, with a combined planned enrollment of more than 28,000 patients. The Phase 3 studies will evaluate Evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia ( LAPLACE-2 ), in patients with hyperlipidemia who cannot tolerate statins ( GAUSS-2 ), as a stand-alone treatment in patients with hyperlipidemia ( MENDEL-2 ), and in patients whose elevated cholesterol is caused by genetic disorders called heterozygous ( RUTHERFORD-2 ) and homozygous ( TESLA and TAUSSIG ) familial hypercholesterolemia.
GAUSS-2 ( Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2 ) is a phase 3 randomized, multicenter, double-blind, placebo- and Ezetimibe-controlled trial designed to evaluate the safety, tolerability and efficacy of Evolocumab in 307 hyperlipidemic patients who could not tolerate effective doses of at least two different statins due to muscle-related side effects.
Patients were randomized to one of four treatment groups: subcutaneous Evolocumab 140 mg every two weeks and oral placebo daily; subcutaneous Evolocumab 420 mg monthly and oral placebo daily; subcutaneous placebo every two weeks and oral Ezetimibe 10 mg daily; or subcutaneous placebo monthly and oral Ezetimibe 10 mg daily.
The co-primary endpoints were the percent reduction from baseline in LDL-C at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. Secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; LDL-C less than 70 mg/dL; and the percentage change from baseline in non-high-density lipoprotein cholesterol ( non-HDL-C ), apolipoprotein B ( ApoB ), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 ( ApoA1 ) ratio, lipoprotein(a), triglycerides, HDL-C and very low-density lipoprotein cholesterol ( VLDL-C ).
Five studies of Evolocumab 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 22,500 patients with cardiovascular disease, DESCARTES ( Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study ) in patients with hyperlipidemia at risk for cardiovascular disease, and 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. ( Xagena )
Source: Amgen, 2014
XagenaMedicine_2014
