FDA Accepts Amgen's Biologics License Application For LDL Cholesterol-Lowering Medication Evolocumab
"There is still a large unmet need among patients with high cardiovascular risk and elevated cholesterol who are unable to reach optimal LDL cholesterol levels with current therapies," said
The BLA, submitted on
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.2,3 Elevated LDL-C is recognized as a major risk factor for cardiovascular disease.4,5 Familial hypercholesterolemia (FH) is an inherited condition caused by genetic mutations which lead to high levels of LDL-C at an early age,6 and it is estimated that less than one percent of people with FH (heterozygous and homozygous forms) in the U.S. are diagnosed.7
Patients can have either one of two types of FH.6 Heterozygous FH is the more common type of FH and occurs globally 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).8 In 2013, the
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
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-C 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, presented and published.
This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the
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The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the
- Amgen Data on File, Investigator Brochure.
World Health Organization. Quantifying Selected Major Risks to Health. In: The World Health Report 2002 - Reducing Risks, Promoting Healthy Life. Geneva. 2002:49-97.
- Merck Manuals website. http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html. Accessed
October 2014. American Heart Association(2012). Why Cholesterol Matters. http://www.heart.org/HEARTORG/Conditions/Cholesterol/WhyCholesterolMatters/Why-Cholesterol-Matters_UCM_001212_Article.jsp. Accessed October 2014. World Health Organization. Global Status Report on Noncommunicable Diseases 2010. Geneva. 2011. National Human Genome Research Institute. Learning About Familial Hypercholesterolemia. http://www.genome.gov/25520184. Accessed October 2014.
- Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial Hypercholesterolaemia is Underdiagnosed and Undertreated in the General Population: Guidance for Clinicians to Prevent Coronary Heart Disease. Eur Heart J. 2013;34:3478-3490.
- Hopkins PN, Toth PP, Ballantyne CM, et al. Familial Hypercholesterolemias: Prevalence, Genetics, Diagnosis and Screening Recommendations From the
National Lipid Association Expert Panelon Familial Hypercholesterolemia. J Clin Lipidol. 2011:5(3S):S9-S17.
- Daniels SR, Samuel SG, de Ferranti SD. Pediatric Aspects of Familial Hypercholesterolemias: Recommendations from the
National Lipid Association Expert Panelon Familial Hypercholesterolemia. J Clin Lipidol. 2011:5(3S):S30-S37.
- Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 Cause Autosomal Dominant Hypercholesterolemia.
Nat Genet. 2003;34:154-156.