THOUSAND OAKS, Calif., Aug. 22, 2016 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that it will present 11 abstracts at the upcoming European Society of Cardiology (ESC) Congress 2016, being held Aug. 27-31 in Rome.
Abstracts include data evaluating Repatha® (evolocumab), a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for the treatment of patients with high cholesterol, across ESC/European Atherosclerosis Society (EAS) cardiovascular risk subgroups, as well as the long-term efficacy and safety of Repatha treatment in patients with the genetic condition heterozygous familial hypercholesterolemia (HeFH). Additionally, an analysis of familial hypercholesterolemia (FH) diagnosis and prevalence will be highlighted as a Rapid Fire Abstract.
"Amgen is committed to further advancing our scientific understanding of Repatha and how it can benefit patients with cardiovascular disease and hypercholesterolemia," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The Repatha clinical development program has clearly demonstrated the medicine's ability to deliver meaningful LDL cholesterol reduction in appropriate patients. The findings presented at ESC 2016, alongside the six new clinical trials that have begun in the last year, will better define the benefit of Repatha for the many patients who continue to struggle with hypercholesterolemia."
Data from Amgen's Center for Observational Research will also be presented, including a presentation on the trends of high-intensity statin therapy after myocardial infarction (MI), as well as research on recurrent coronary heart disease and mortality risk following MI, in medically-managed patients. In addition, Amgen Global Health Economics data from a multi-ethnic study will be presented on the residual risks of atherosclerotic cardiovascular disease (ASCVD) in statin-treated adults.
Amgen-sponsored abstracts at ESC Congress 2016 include:
- Efficacy of evolocumab in patients across ESC/EAS CV risk subgroups
Abstract 061051, Poster Presentation, Sunday, Aug. 28, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Pharmacokinetics and pharmacodynamics of evolocumab in patients with renal impairment
Abstract 055112, Poster Presentation, Sunday, Aug. 28, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolaemia
Abstract 060215, Poster Presentation, Sunday, Aug. 28, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Factorial effects of evolocumab and atorvastatin on lipoprotein metabolism: the FLOREY stable isotope study
Abstract 061052, Poster Presentation, Monday, Aug. 29, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Familial hypercholesterolaemia diagnosis: a case of missed opportunity
Abstract 060852, Rapid Fire Abstract, Saturday, Aug. 27, 11:27-11:45 a.m. CET (Agora 2- Poster Area)
- Trends in high-intensity statin therapy after myocardial infarction, 2011-2014
Abstract 060217, Poster Presentation, Sunday, Aug. 28, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Increased recurrent coronary heart disease and mortality risk among intensive medically managed patients following myocardial infarction
Abstract 061617, Poster Presentation, Monday, Aug. 29, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Statin use and dose by low-density lipoprotein cholesterol level in U.S. commercially insured patients with type 2 diabetes
Abstract 061615, Moderated Poster Presentation, Tuesday, Aug. 30, 10:12-10:19 a.m. CET (Moderated Poster Station - Poster Area)
- Prevalence of patients with familial hypercholesterolemia (FH) in the German cardiology office-based setting
Abstract 059510, Poster Presentation, Monday, Aug. 29, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Contemporary low-density lipoprotein-cholesterol (LDL-C) levels and patient characteristics in 1000 high-risk patients examined in German cardiology practices
Abstract 059515, Poster Presentation, Monday, Aug. 29, 8:30 a.m.-12:30 p.m. CET (Poster Area)
- Residual atherosclerotic cardiovascular disease risk in statin-treated adults: the multi-ethnic study of atherosclerosis
Abstract 061097, Moderated Poster Presentation, Tuesday, Aug. 30, 10:40-10:47 a.m. CET (Moderated Poster Station - Poster Area)
New Repatha Clinical Trials
The below list of clinical trials have begun enrolling patients since Sept. 1, 2015:
- A Double-blind, Randomized Study in Diabetic Subjects With Hyperlipidemia or Mixed Dyslipidemia
- Trial Assessing Efficacy, Safety and Tolerability of PCSK9 Inhibition in Paediatric Subjects With Genetic LDL Disorders (HAUSER-RCT)
- A Study in Subjects With Type 2 Diabetes Mellitus With Hypercholesterolemia/Mixed Dyslipidemia
- Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition on Arterial Wall Inflammation Study in Patients With Elevated Lipoprotein(a) (Lp(a)). (ANITSCHKOW)
- Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4
- Trial Assessing Evolocumab(AMG145) Compared to LDL-C Apheresis in Subjects Receiving LDL-C Apheresis Prior to Study Enrollment
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
GLAGOV, the intravascular ultrasound study, is underway to determine the effect of Repatha on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization to test the hypothesis of robust LDL-C reduction leading to a reduction or a change in the build-up of plaque in the arteries. Results from the GLAGOV study are expected in the second half of 2016.
The FOURIER outcomes trial is designed to evaluate whether treatment with Repatha in combination with statin therapy, compared to placebo plus statin therapy, reduces the risk of cardiovascular events in patients with high cholesterol and clinically evident cardiovascular disease, and completed patient enrollment in June 2015. The primary endpoint for the FOURIER trial is major cardiovascular events defined as the composite of cardiovascular death, myocardial infarction (MI), stroke, hospitalization for unstable angina or coronary revascularization. The key secondary end point is the composite of cardiovascular death, MI or stroke. The trial is planned to continue until at least 1,630 patients experience the secondary endpoint, thereby providing 90 percent power to detect a relative reduction of 15 percent in this endpoint. Top-line results from the approximately 27,500-patient event-driven FOURIER study are anticipated in first quarter of 2017.
Repatha is approved in 44 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 EU Product Information
Repatha® is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:
- In combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or,
- Alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
Repatha® is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies.
The effect of Repatha® on cardiovascular morbidity and mortality has not yet been determined.
Important EU Safety Information
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Posology: The recommended dose for adults with primary disease is either 140 mg every two weeks or 420 mg (the contents of three pre-filled syringes) once a month; both doses are clinically equivalent. For adults or children older than 12 years with homozygous familial hypercholesterolemia, the initial recommended dose is 420 mg once a month. If a response is not achieved after 12 weeks of treatment, the dose can be increased up to 420 mg every two weeks. For more information, see the package leaflet.
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Special Warnings and Precautions: Renal impairment: Patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m2) have not been studied. Repatha should be used with caution in patients with severe renal impairment. Hepatic impairment: In patients with moderate hepatic impairment, a reduction in total evolocumab exposure was observed that may lead to a reduced effect on LDL-C reduction. Therefore, close monitoring may be warranted in these patients. Patients with severe hepatic impairment (Child-Pugh C) have not been studied. Repatha should be used with caution in patients with severe hepatic impairment. Dry natural rubber: The needle cover of the glass pre-filled syringe and of the pre-filled pen is made from dry natural rubber (a derivative of latex), which may cause allergic reactions. Sodium content: Repatha contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially 'sodium-free.'
Interactions: No formal drug-drug interaction studies have been conducted for Repatha. No studies on pharmacokinetic and pharmacodynamics interaction between Repatha and lipid-lowering drugs other than statins and ezetimibe have been conducted.
Fertility, Pregnancy and Lactation: There are no or limited amount of data from the use of Repatha in pregnant women. Repatha should not be used during pregnancy unless the clinical condition of the woman requires treatment with evolocumab. It is unknown whether evolocumab is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded. No data on the effect of evolocumab on human fertility are available.
Undesirable Effects: The following common (≥ 1/100 to < 1/10) adverse reactions have been reported in pivotal, controlled clinical studies: influenza, nasopharyngitis, upper respiratory tract infection, rash, nausea, back pain, arthralgia, injection site reactions. Please consult the SmPC for a full description of undesirable effects.
Pharmaceutical Precautions: Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the pre-filled syringe or the pre-filled pen in the original carton in order to protect from light. If removed from the refrigerator, Repatha may be stored at room temperature (up to 25°C) in the original carton and must be used within 1 week.
Important U.S. Product Information
Repatha® is indicated as an adjunct to diet and:
- Maximally tolerated statin therapy for treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low-density lipoprotein cholesterol (LDL-C)
- 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 effect of Repatha® on cardiovascular morbidity and mortality has not been determined.
The safety and effectiveness of Repatha® have not been established in pediatric patients with HoFH who are younger than 13 years old.
The safety and effectiveness of Repatha® have not been established 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% of Repatha® -treated patients and more common than placebo) 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% of Repatha® -treated patients and 1% 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% versus 0% 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% and 3.0% 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% and 0%, respectively.
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%).
Neurocognitive events were reported in less than or equal to 0.2% in Repatha®-treated and placebo-treated patients.
In a pool of placebo- and active-controlled trials, as well as open-label extension studies that followed them, a total of 1,988 patients treated with Repatha® had at least one LDL-C value <25 mg/dL. Changes to background lipid-altering therapy were not made in response to low LDL-C values, and Repatha® dosing was not modified or interrupted on this basis. Although adverse consequences of very low LDL-C were not identified in these trials, the long-term effects of very low levels of LDL-C induced by Repatha® are unknown.
Musculoskeletal adverse reactions were reported in 14.3% of Repatha® -treated patients and 12.8% of placebo-treated patients. The most common adverse reactions that occurred at a rate greater than placebo were back pain (3.2% versus 2.9% for Repatha® and placebo, respectively), arthralgia (2.3% versus 2.2%), and myalgia (2.0% versus 1.8%).
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%) Repatha®-treated patients and more frequently than in placebo-treated patients, included upper respiratory tract infection (9.1% versus 6.3%), influenza (9.1% versus 0%), gastroenteritis (6.1% versus 0%), and nasopharyngitis (6.1% versus 0%).
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 Cardiovascular
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.
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 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.
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CONTACT: Amgen, Thousand Oaks
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- Repatha® U.S. Prescribing Information. Amgen.
- World Health Organization. Cardiovascular diseases (CVDs) fact sheet. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed July 2016.