New Detailed Data From Phase 3 Study Show Amgen’s Repatha™ (Evolocumab) In Combination With Statins Reduced LDL-C By 67-76 Percent Compared To Placebo In Japanese Patients With High Cardiovascular Risk And High CholesterolData From PCSK9 Inhibitor Study Support Regulatory Filing in Japan
Amgen (AMGN) today announced new detailed data from the Phase 3 YUKAWA-2 study evaluating Repatha™ (evolocumab), a novel investigational cholesterol-lowering medication, in Japanese patients with high cardiovascular risk and high cholesterol. Data from the study showed subcutaneous Repatha 140 mg every two weeks or 420 mg monthly, compared to placebo, in combination with different daily doses of atorvastatin, reduced low-density lipoprotein cholesterol (LDL-C) by 67 to 76 percent from baseline at week 12 and at the mean of weeks 10 and 12. The data were presented at the American College of Cardiology’s 64th Annual Scientific Session (ACC.15).
In the YUKAWA-2 study, the most common adverse events that occurred in greater than 2 percent of the Repatha group were nasopharyngitis (16.8 percent Repatha; 17.8 percent placebo), gastroenteritis (3.0 percent Repatha; 1.0 percent placebo) and pharyngitis (2.5 percent Repatha; 2.5 percent placebo).
“The positive results from this study in Japan add to the consistent findings we have seen with Repatha across patient populations in our comprehensive clinical program,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “Statins are an important therapy for patients with high cholesterol and adding Repatha may help lower their LDL cholesterol levels when statins are not sufficient. We look forward to working with regulatory authorities in Japan to bring this new investigational medication to patients.”
Repatha 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 LDL-C, or “bad” cholesterol, from the blood.1 In Japan, LDL-C levels are not adequately controlled for many high-risk patients taking statins, nearly half of whom have not reached their LDL-C goal.2,3
“Statins are a cornerstone of treatment for people with high cholesterol who are unable to lower their LDL cholesterol to appropriate levels despite efforts to improve diet and exercise,” said Arihiro Kiyosue, Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan, and Tokyo-Eki Center-building Clinic, Tokyo, Japan, and investigator for the YUKAWA-2 study. “We are encouraged by the results from the Phase 3 YUKAWA-2 study, which show that adding evolocumab to stable statin therapy in high-risk patients further reduced LDL cholesterol.”
High cholesterol is the most common form of dyslipidemia, which is an abnormality of cholesterol and/or fats in the blood.4,5 There are approximately 300 million cases of dyslipidemia in the U.S., Japan and Western Europe.6
YUKAWA-2 Study Design
YUKAWA-2 (StudY of LDL-Cholesterol Reduction Using a Monoclonal PCSK9 Antibody in Japanese Patients With Advanced Cardiovascular Risk) is a Phase 3, multicenter, double-blind, randomized, placebo-controlled trial designed to evaluate the safety, tolerability and efficacy of Repatha™ (evolocumab) in 404 Japanese patients with high cardiovascular risk based on the Japan Atherosclerosis Society guidelines2 and with hyperlipidemia or mixed dyslipidemia (LDL-C >100 mg/dL). Patients were randomized to one of eight treatment groups in a two-step randomization. Eligible patients were initially randomized to one of the following background therapies: atorvastatin 5 mg daily or atorvastatin 20 mg daily and entered a four-week lipid stabilization period. At completion of lipid stabilization, patients were then randomized to one of four treatment arms: Repatha 140 mg every two weeks, Repatha 420 mg monthly, subcutaneous placebo every two weeks or subcutaneous placebo monthly. 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. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: LDL-C
Amgen Webcast Investor Call
Amgen will host a webcast investor call on Monday, March 16, at 1 p.m. PT. Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team, will participate in the call to discuss Amgen’s cardiovascular program, including Repatha data presented at ACC.15.
Live audio of the investor meeting will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public.
The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.
About Repatha™ (Evolocumab)
Repatha™ (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.7 Repatha, 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
The FDA has provisionally approved the trade name Repatha.
Repatha is developed in Japan by Amgen Astellas BioPharma K.K., a joint venture between Amgen and Astellas Pharma Inc., a pharmaceutical company headquartered in Tokyo, Japan.
About PROFICIO: Repatha™ (Evolocumab) Clinical Trial Program
PROFICIO, which stands for the Program to Reduce LDL-C and CardiovascularOutcomes Following Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating Repatha™ (evolocumab) in 22 clinical trials, with a combined planned enrollment of approximately 35,000 patients.
The Phase 3 program includes 16 trials to evaluate Repatha 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 Repatha on lipoprotein metabolism (FLOREY); and the administration of Repatha in statin-treated hyperlipidemic patients (THOMAS-1 and THOMAS-2).
Five ongoing studies in the Repatha 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 Repatha 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 Repatha 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 (GLobalAssessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of Repatha 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 Repatha 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.
About Amgen’s Commitment to Cardiovascular Disease
Amgen is dedicated to addressing important scientific questions in order to advance care and improve the lives of patients with cardiovascular disease. Through its own research and development efforts and innovative partnerships, Amgen has built a robust cardiology pipeline consisting of several investigational molecules in an effort to address a number of today’s important unmet patient needs, such as high cholesterol and heart failure.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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 Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen’s most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen’s most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of March 14, 2015, and expressly disclaims any duty to update information contained in this news release.
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CONTACT: Amgen, Thousand Oaks
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- Amgen Data on File, Investigator Brochure.
- Teramoto T, Sasaki J, Ishibashi S, et al. Executive Summary of the Japan Atherosclerosis Society (JAS) Guidelines for the Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases in Japan – 2012 version. J Atheroscler Thromb. 2013;20(6):517-523.
- Teramoto T, Kashiwagi A, Ishibashi S, Daida H. Cross-Sectional Survey to Assess the Status of Lipid Management in High-Risk Patients With Dyslipidemia: Clinical Impact of Combination Therapy With Ezetimibe. Current Therapeutic Research. 2013;73(1-2).
- World Health Organization. Quantifying Selected Major Risks to Health. In: The World Health Report 2002 – Reducing Risks, Promoting Healthy Life. Chapter 4: Geneva: World.
- Merck Manuals website.http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html. Accessed February 2015.
- National Institute of Health (2009). Federal Register Volume 74 (250). Washington, DC: U.S. Government Printing Office. http://www.gpo.gov/fdsys/pkg/FR-2009-12-31/html/E9-31072.htm. Accessed February 2015.
- Abifadel M et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-156.
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