THOUSAND OAKS, Calif., Aug. 28, 2014 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for evolocumab seeking approval for the treatment of high cholesterol. Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, from the blood. 1
The BLA for evolocumab contains data from approximately 6,800 patients, including more than 4,500 patients with high cholesterol in 10 Phase 3 trials. The Phase 3 studies evaluated the safety and efficacy of evolocumab in patients with elevated cholesterol on statins with or without other lipid-lowering therapies; patients who cannot tolerate statins; patients with heterozygous familial hypercholesterolemia (HeFH); and patients with homozygous familial hypercholesterolemia (HoFH), a rare and serious genetic disorder. 2
"This BLA submission to the FDA marks the first of several submissions to regulatory authorities around the world for our lipid-lowering program and represents a critical milestone in our overall global development program for evolocumab," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to working closely with regulatory authorities to bring this new treatment option to patients with high cholesterol who, despite currently available therapies, are unable to adequately reduce their LDL cholesterol levels."
High cholesterol, particularly elevated LDL-C, is the most common form of dyslipidemia, which is an abnormality of cholesterol and/or fats in the blood. 3,4 Elevated LDL-C is recognized as a major risk factor for cardiovascular disease. 5,6 Familial hypercholesterolemia (FH) is an inherited condition caused by genetic mutations which lead to high levels of LDL-C at an early age, 2 and it is estimated that less than one percent of people with FH (heterozygous and homozygous forms) in the U.S. are diagnosed. 7Patients can have either one of two types of FH. 1 Heterozygous FH is the more common type of FH and occurs in approximately one in 200 to 500 people. 7 It can cause LDL-C levels twice as high as normal (e.g., >190 mg/dL). 8 Individuals with HeFH have one altered copy of a cholesterol-regulating gene. 8 Homozygous FH is the rare, more severe form, occurring in approximately one in a million individuals. 9 It can cause LDL-C levels more than six times as high as normal (e.g., 650-1,000 mg/dL). 9 An individual with HoFH has two altered copies of cholesterol-regulating genes (one from each parent). 2 In 2013, the FDA granted evolocumab an orphan drug designation for HoFH. About Evolocumab Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). 1 PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood. 10 Evolocumab, being developed by Amgen scientists, 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. 1 About PROFICIO: The Evolocumab Clinical Trial Program PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of P CSK9 In Different P Opulations, is a large and comprehensive clinical trial program evaluating evolocumab in 22 clinical trials, with a combined planned enrollment of approximately 30,000 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).