Amgen Submits BLA for Novel Investigational LDL Cholesterol-Lowering Medication Evolocumab to FDA

Amgen has announced the submission of a Biologics License Application (BLA) to 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 6800 patients, including more than 4500 patients with high cholesterol in 10 Phase III trials. The Phase 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.

"This BLA submission to 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, MD, 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. Elevated LDL-C is recognised 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 1% of people with FH (heterozygous and homozygous forms) in the US 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., >190 mg/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, FDA granted evolocumab an orphan drug designation for HoFH.