THOUSAND OAKS, Calif. (Nov. 13, 2020) - Amgen (NASDAQ:AMGN) today announced a new analysis from the Repatha® (evolocumab) cardiovascular (CV) outcomes study (FOURIER) that evaluated the effectiveness of Repatha in atherosclerotic cardiovascular disease (ASCVD) patients on statin therapy with prior percutaneous coronary intervention (PCI), also known as coronary angioplasty. The analysis showed that Repatha reduced the risk of CV events by 18% in patients with prior PCI, who were at a very high risk for CV events compared to patients with no prior PCI. The results were presented at the American Heart Association (AHA) Scientific Sessions 2020: A Virtual Experience, Nov. 13-17, 2020.
"Despite statin therapy, patients in this analysis with prior PCI had a 50% higher chance of having another major coronary event, including revascularization, than patients with no history of PCI," said Brian A. Bergmark, M.D., associate physician in interventional cardiology in the Division of Cardiovascular Medicine at Brigham and Women's Hospital and a FOURIER study investigator at the TIMI Study Group. "This analysis shows the benefit of PCSK9 inhibition with evolocumab in reducing major coronary events in patients who have undergone PCI and may provide information for interventional cardiologists to consider as a part of their treatment regimen for secondary prevention."
In this analysis of the FOURIER study, ASCVD patients on statin therapy with prior PCI, in comparison to those without prior PCI, had nearly double the rate of major coronary events (14.5% vs. 7.8%, respectively), and Repatha reduced the rate of these events by 18% (11.7% vs. 14.5%, respectively). Repatha, when added to statin therapy, reduced the percentage of patients requiring revascularization (7.2% vs. 9.3%, respectively), including new PCI, PCI for de novo lesions, PCI for not de novo lesions and revascularization for in-stent restenosis, in comparison with placebo. At three years with Repatha, the absolute risk reduction for major coronary events was 2.8% in patients with prior PCI versus 0.3% in those without, with a number needed to treat (NNT) at three years of only 36 in prior-PCI patients receiving Repatha in comparison with placebo. The observed hazard ratio for CV death from the FOURIER primary analysis was 1.05 (95% CI, 0.88-1.25).
"These data demonstrate the importance of lipid-lowering therapy for secondary prevention in this subpopulation of high-risk patients and reinforce Repatha's ability to significantly reduce CV events for patients who are in need of more intensive lipid management beyond statins alone to achieve LDL-C guideline standards and improve patient outcomes," said David M. Reese, M.D., executive vice president of Research and Development at Amgen.
New Network Meta-Analysis Highlights Most Efficacious Non-Statin Lipid-Lowering Therapies
A network meta-analysis of 48 randomized clinical trials assessing the relative efficacy of non-statin lipid-lowering therapies in reducing LDL-C levels when added to statin therapy was also presented at AHA 2020. Over 12 weeks, all non-statin lipid-lowering therapies significantly reduced LDL-C from baseline in comparison with placebo. The PCSK9 inhibitor regimens of Repatha 140 mg once every two weeks (Q2W) or 420 mg once monthly (QM) and alirocumab 150 mg Q2W were the most effective for reducing LDL-C levels when added to statins. Specifically, Repatha demonstrated a 64% LDL-C reduction from baseline to week 12 in comparison to placebo. This analysis suggests that when statins alone are insufficient, the addition of the most efficacious PCSK9 inhibitor regimen is the best approach to helping very high risk patients achieve the lower LDL-C goals recommended in clinical guidelines.
FOURIER randomized 27,564 patients with established ASCVD, additional high risk criteria and LDL-C >70 mg/dL on statin therapy to Repatha (140 mg Q2W or 420 mg once every four weeks (Q4W)) or matching placebo, with a median follow-up of 2.2 years. Patients with priory history of PCI were a pre-specified subgroup of interest. At baseline, 17,073 (62%) patients had a prior PCI. The primary end point was time to major coronary events (composite of CV death, myocardial infarction (MI), stroke, unstable angina or coronary revascularization); major coronary events (composite of death due to coronary disease, MI or coronary revascularization) comprised a secondary endpoint of interest. All endpoints were blindly adjudicated by an independent clinical events committee. Reports of coronary revascularization events were blindly reviewed to extract granular data on coronary revascularization procedures. Prior PCI and non-PCI groups were compared for the aforementioned endpoints within the placebo arm, with a multivariable Cox proportional hazards model to adjust for baseline differences. Efficacy of Repatha versus placebo was compared, stratified according to prior history of PCI, to evaluate the reduction of major CV events and coronary revascularization.
About the Repatha Cardiovascular Outcomes (FOURIER) Study
FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a multinational Phase 3 randomized, double-blind, placebo-controlled trial, is designed to evaluate whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces cardiovascular events. The primary endpoint is the time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint is the time to cardiovascular death, myocardial infarction or stroke.
Eligible patients with high cholesterol (LDL-C ≥70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] ≥100 mg/dL) and clinically evident ASCVD at more than 1,300 study locations around the world were randomized to receive Repatha subcutaneous 140 mg every two weeks or 420 mg monthly plus effective statin dose; or placebo subcutaneous every two weeks or monthly plus effective statin dose. Optimized statin therapy was defined as at least atorvastatin 20 mg or equivalent daily with a recommendation for at least atorvastatin 40 mg or equivalent daily where approved. The study was event-driven and continued until at least 1,630 patients experienced a key secondary endpoint.
FOURIER is part of Amgen's PROFICIO (Program to Reduce LDL-C and cardiovascular Outcomes Following Inhibition of PCSK9 In different pOpulations) program of clinical studies investigating the impact of Repatha on LDL-C and CVD across multiple populations at high cardiovascular risk, including those managed by statins, statin-intolerant patients, those with genetic disorders and patients with atherosclerosis. To date, the PROFICIO program consists of 50 trials including more than 43,000 patients worldwide.
About Repatha® (evolocumab)
Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels
Repatha is approved in more than 75 countries, including the U.S., Japan, Canada, Australia, China and in all 28 countries that are members of the European Union. Applications in other countries are pending.
Important U.S. Product Information
Repatha is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor antibody indicated:
- to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
- as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) to reduce low-density lipoprotein cholesterol (LDL-C).
- as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.
The safety and effectiveness of Repatha have not been established in pediatric patients with HoFH who are younger than 13 years old or in pediatric patients with primary hyperlipidemia or HeFH.
Repatha is contraindicated in patients with a history of a serious hypersensitivity reaction to Repatha. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha.
Hypersensitivity reactions (e.g. angioedema, rash, urticaria) have been reported in patients treated with Repatha, including some that led to discontinuation of therapy. If signs or symptoms of serious allergic reactions occur, discontinue treatment with Repatha, treat according to the standard of care, and monitor until signs and symptoms resolve.
The most common adverse reactions (>5% of patients treated with Repatha and occurring more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising.
Allergic reactions occurred in 5.1% and 4.7% of Repatha-treated and placebo-treated patients, respectively. The most common allergic reactions were rash (1.0% versus 0.5% for Repatha and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
The most common adverse reactions in the Cardiovascular Outcomes Trial (>5% of patients treated with Repatha and occurring more frequently than placebo) were: diabetes mellitus (8.8% Repatha, 8.2% placebo), nasopharyngitis (7.8% Repatha, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients assigned to Repatha compared with 7.7% in those assigned to placebo.
Homozygous Familial Hypercholesterolemia (HoFH):
The adverse reactions that occurred in at least two patients treated with Repatha and more frequently than placebo were: upper respiratory tract infection, influenza, gastroenteritis, and nasopharyngitis.
Repatha is a human monoclonal antibody. As with all therapeutic proteins, there is a potential for immunogenicity with Repatha.
Please contact Amgen Medinfo at 800-77-AMGEN (800-772-6436) or 844-REPATHA (844-737-2842) regarding Repatha® availability or find more information, including full Prescribing Information, at http://www.amgen.com and http://www.Repatha.com.
About Amgen in the Cardiovascular Therapeutic Area
Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses, Amgen is dedicated to addressing important scientific questions to advance care and improve the lives of patients with cardiovascular disease, the leading cause of morbidity and mortality worldwide. Amgen's research into cardiovascular disease, and potential treatment options, is part of a growing competency at Amgen that utilizes human genetics to identify and validate certain drug targets. Through its own research and development efforts, as well as partnerships, Amgen is building a robust cardiovascular portfolio consisting of several approved and 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 the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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1. World Health Organization. Cardiovascular diseases (CVDs) fact sheet.
Accessed September 2020.