Additional FOURIER Analysis Shows Lowering LDL-C With Repatha Did Not Impair Patient-Reported Cognition
THOUSAND OAKS, Calif. (Nov. 16, 2019) – Amgen today announced a new analysis from the Repatha® (evolocumab) cardiovascular outcomes (FOURIER) study that evaluates the effectiveness of Repatha in patients who have suffered a recent myocardial infarction (MI). The analysis showed that patients who experienced a recent MI (less than one year) were at higher risk of subsequent cardiovascular (CV) events compared to patients who had an MI over a year ago. In the analysis, the risk reduction for experiencing a heart attack, stroke or CV death, in Repatha-treated patients treated within one year post MI was 25% compared to 15% in those patients with a more distant MI. The results will be presented at the American Heart Association Annual Scientific Sessions in Philadelphia on Monday, Nov. 18.
“Nearly 1 in 5 patients will have a recurrent CV event during the first year after a heart attack which makes that year a critical time for high-risk patients1,” said Robert Giugliano, M.D., FOURIER executive committee member and a senior investigator at the TIMI Study Group at Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School. “These results demonstrate the importance of intensive lipid-lowering therapy in the first year following a heart attack and provide additional evidence that evolocumab significantly reduces CV risk and improves outcomes for high-risk patients.”
In this analysis of the landmark FOURIER outcomes study, 5,711 patients who experienced an MI within one to 12 months of randomization were compared to 16,609 patients with a more distant event (>12 months prior to randomization) to assess the efficacy of Repatha on the primary endpoint (CV death, MI, stroke, unstable angina or coronary revascularization) and the key secondary endpoint (CV death, MI or stroke).
“Far too many patients remain at risk of another CV event because they are not managing one of the most important modifiable risk factors for a heart attack: high LDL-C2,” said Darryl Sleep, M.D., senior vice president of Global Medical and chief medical officer at Amgen. “These data demonstrate the important role cardiologists play in closely monitoring and managing LDL-C in high-risk patients, and support recent professional guideline recommendations that call for more intensive reduction of LDL-C to lower the risk of future CV events in high-risk patients3,4.”
New FOURIER Data Shows No Impact on Patient-Reported Cognition Function
An additional analysis from the FOURIER study presented at AHA reinforces the safety and efficacy of intensive LDL-C lowering with Repatha in high-risk cardiovascular disease (CVD) patients. The analysis evaluated the impact of lowering LDL-C with Repatha on cognition as reported by patients with stable CVD and found that the addition of Repatha to statin therapy had no impact on reported everyday cognition function, including in those with very low LDL-C levels.
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 CV risk, including those managed by statins, statin-intolerant patients, those with genetic disorders and patients with atherosclerosis. To date, the PROFICIO program consists of 36 trials including more than 38,000 patients worldwide.
Repatha Cardiovascular Outcomes (FOURIER) Study Design
FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a multinational Phase 3 randomized, double-blind, placebo-controlled trial, was designed to evaluate whether treatment with Repatha in combination with statin therapy compared to placebo plus statin therapy reduces cardiovascular events. The primary endpoint was the time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint was 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 atherosclerotic cardiovascular disease 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.
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.5
Repatha is approved in more than 70 countries, including the U.S., Japan, Canada 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.
Important U.S. Safety Information
Contraindication: 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.
Allergic reactions: 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.
Adverse reactions: 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.
Immunogenicity: 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 www.amgen.com and 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.6 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.
1. Jernberg T, et al. Eur Heart J. 2015;36:1163-1170.
2. Goldstein JL, et al. Arterioscler Thromb Vasc Biol. 2009;29(4):431-438.
3. Mach F, et al. European Heart Journal. 2019;ehz455. https://doi.org/10.1093/eurheartj/ehz455
4. Grundy SM, et al. JACC. 2018; 1-80.
5. Repatha Prescribing Information; Amgen, Thousand Oaks, CA, 2018.
6. World Health Organization. Cardiovascular diseases (CVDs) fact. sheet. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed November 2019.