Amgen has submitted a Biologics License Application (BLA) to the 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.
The BLA for evolocumab contains data from approximately 6,800 patients, including more than 4,500 patients with high cholesterol in 10 phase III trials. The III 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.
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. Elevated LDL-C is recognized as a major risk factor for cardiovascular disease. Familial hypercholesterolemia (FH) is an inherited condition caused by genetic mutations which lead to high levels of LDL-C at an early age, and it is estimated that less than one percent of people with FH (heterozygous and homozygous forms) in the U.S. are diagnosed.
Patients can have either one of two types of FH. Heterozygous FH is the more common type of FH and occurs in approximately one in 200 to 500 people. It can cause LDL-C levels twice as high as normal (e.g., >190mg/dL). Individuals with HeFH have one altered copy of a cholesterol-regulating gene.
Homozygous FH is the rare, more severe form, occurring in approximately one in a million individuals. It can cause LDL-C levels more than six times as high as normal (e.g., 650-1,000
mg/dL). An individual with HoFH has two altered copies of cholesterol-regulating genes (one from each parent). In 2013, the FDA granted evolocumab an Orphan Drug designation for HoFH.