"The depth and breadth of our clinical trial program continues to highlight different patient groups that may benefit from intensive LDL-C reduction with Repatha," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to sharing data showing the likelihood of coronary atherosclerosis regression with Repatha treatment, as well as results from the Repatha cardiovascular outcomes study evaluating efficacy in patients with residual inflammation."
A full listing of Amgen-related abstracts at ACC.18 include:
Moderated Poster Theaters:
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, is designed to evaluate whether treatment with Repatha in combination with high- or moderate-intensity statin therapy compared to placebo plus statin therapy reduces cardiovascular events. The hard MACE composite endpoint is the time to cardiovascular death, myocardial infarction or stroke (key secondary endpoint). The extended MACE composite endpoint is the time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization (primary endpoint).
Eligible patients with high cholesterol (LDL-C ≥70 mg/dL or non-high-density lipoprotein cholesterol [non-HDL-C] ≥100 mg/dL) and established 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 high- or moderate-intensity effective statin dose; or placebo subcutaneous every two weeks or monthly plus high- to moderate-intensity statin dose. Statin therapy was defined in the protocol 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.
GLAGOV Study Design
GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound) is a Phase 3, multicenter, double-blind, randomized, placebo-controlled trial designed to evaluate the effect of Repatha on the change in burden of coronary artery disease (CAD) in 968 patients undergoing clinically indicated coronary angiogram and on optimized background statin therapy.
Patients were required to have been treated with a stable statin dose for at least four weeks and to have a LDL-C ≥80 mg/dL or between 60 and 80 mg/dL with one major cardiovascular risk factor (defined as non-coronary atherosclerotic vascular disease, myocardial infarction or hospitalization for unstable angina in the preceding two years or type 2 diabetes mellitus) or three minor cardiovascular risk factors (defined as current cigarette smoking, hypertension, low levels of HDL cholesterol, family history of premature coronary heart disease, high sensitivity C-reactive protein (hs-CRP) ≥2 mg/L or age ≥50 years in men and 55 years in women).
Patients were randomized 1:1 into two treatment groups to either receive monthly Repatha 420 mg or placebo subcutaneous injections. Optimized statin therapy was defined as at least atorvastatin 20 mg daily or equivalent, titrated to achieve LDL-C reduction per regional guidelines. Highly effective statin therapy (equivalent to atorvastatin 40 mg daily or higher) was recommended for all patients. Those patients with LDL-C >100 mg/dL not taking highly effective statin therapy, required investigators' attestation as to why such doses were not appropriate. The primary endpoint was change in percent atheroma volume (PAV) from baseline to week 78 compared to placebo, as determined by intravascular ultrasound (IVUS). IVUS is a high-resolution imaging tool that allows for the quantification of coronary atheroma in the coronary arteries.
Secondary endpoints included PAV regression (any reduction from baseline); change in total atheroma volume (TAV) from baseline to week 78; and regression (any reduction from baseline) in TAV.
About Repatha® (evolocumab)
Repatha® (evolocumab) 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.1
Repatha is approved in more than 50 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.
U.S. Repatha Indication
Repatha is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor antibody indicated:
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.
Allergic reactions: Hypersensitivity reactions (e.g. 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 percent of Repatha-treated patients and occurring more frequently than placebo) in controlled trials involving patients with primary hyperlipidemia, including HeFH, were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
In a 52-week trial, adverse reactions led to discontinuation of treatment in 2.2 percent of Repatha-treated patients and 1 percent of placebo-treated patients. The most common adverse reaction that led to Repatha treatment discontinuation and occurred at a rate greater than placebo was myalgia (0.3 percent versus 0 percent for Repatha and placebo, respectively).
Adverse reactions from a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2 percent and 3.0 percent of Repatha-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising. The proportions of patients who discontinued treatment due to local injection site reactions in Repatha-treated patients and placebo-treated patients were 0.1 percent and 0 percent, respectively.
Allergic reactions occurred in 5.1 percent and 4.7 percent of Repatha-treated and placebo-treated patients, respectively. The most common allergic reactions were rash (1.0 percent versus 0.5 percent for Repatha and placebo, respectively), eczema (0.4 percent versus 0.2 percent), erythema (0.4 percent versus 0.2 percent), and urticaria (0.4 percent versus 0.1 percent).
The safety profile of Repatha in the cardiovascular outcomes trial was generally consistent with the safety profile in the 12- and 52-week controlled trials involving patients with primary hyperlipidemia, including HeFH. Serious adverse events occurred in 24.8 percent and 24.7 percent of Repatha-treated and placebo-treated patients, respectively. Adverse events led to discontinuation of study treatment in 4.4 percent of patients assigned to Repatha and 4.2 percent assigned to placebo. Common adverse reactions (>5 percent of patients treated with Repatha and occurring more frequently than placebo) included diabetes mellitus (8.8 percent Repatha, 8.2 percent placebo), nasopharyngitis (7.8 percent Repatha, 7.4 percent placebo) and upper respiratory tract infection (5.1 percent Repatha, 4.8 percent placebo). Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1 percent in patients assigned to Repatha compared with 7.7 percent in those assigned to placebo.
Homozygous Familial Hypercholesterolemia (HoFH): In 49 patients with homozygous familial hypercholesterolemia studied in a 12-week, double-blind, randomized, placebo-controlled trial, 33 patients received 420 mg of Repatha subcutaneously once monthly. The adverse reactions that occurred in at least 2 (6.1 percent) Repatha-treated patients and more frequently than in placebo-treated patients, included upper respiratory tract infection (9.1 percent versus 6.3 percent), influenza (9.1 percent versus 0 percent), gastroenteritis (6.1 percent versus 0 percent), and nasopharyngitis (6.1 percent versus 0 percent).
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.2 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.
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CONTACT: Amgen, Thousand Oaks
Repatha® U.S. Prescribing Information. Amgen.
World Health Organization. Cardiovascular diseases (CVDs) fact sheet. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed October 30, 2017.
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