Repatha (Evolocumab) Late-Breaking Data Showcase First Phase 3 Study of a PCSK9 Inhibitor in Pediatric Heterozygous Familial Hypercholesterolemia
New Data Highlight Gaps in Treating High LDL-C to Clinical Treatment Guidelines in a Large Cohort of European, High-Risk CVD Patients
THOUSAND OAKS, Calif., Aug. 25, 2020 /PRNewswire/ — Amgen (NASDAQ:AMGN) today announced the presentation of 12 cardiovascular scientific research abstracts, including clinical trial and real-world evidence studies of Repatha® (evolocumab), that add to the growing body of evidence demonstrating the efficacy and safety of Repatha and the importance of managing high-risk patients in accordance with global treatment guidelines. The data will be presented at ESC Congress 2020 – The Digital Experience, organized by the European Society of Cardiology, Aug. 29–Sept. 1.
Notable abstracts include data from the first randomized controlled Phase 3 study of a PCSK9 inhibitor, Repatha, in pediatric patients with heterozygous familial hypercholesterolemia (HeFH), which will be presented as a late-breaking abstract in an oral presentation. HeFH is a genetic disorder that affects approximately 1 in 250 individuals globally and results in high levels of low-density lipoprotein cholesterol (LDL-C) at a very young age despite treatment with statins and other cholesterol-lowering therapies.1,2 With HeFH, there is an accelerated development and increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD).3
A separate study across 18 European countries described how lipid-lowering therapy (LLT) is used for primary and secondary prevention of ASCVD and assessed how current practice impacts LDL-C goals recommended by the ESC/EAS guidelines. A third study across 10 European countries evaluated the reduction of LDL-C by the real-world use of Repatha in patients at very high-risk for a cardiovascular event and simulated the associated 10-year cardiovascular risk and risk reduction relative to baseline.
“The depth and breadth of data we are sharing with the scientific community reflects our commitment to developing and delivering transformative medicines that improve the lives of patients, including pediatric patients with genetically high LDL-C, who are at high lifetime risk for cardiovascular events,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “We are addressing the ongoing unmet need in LDL-C by understanding how Repatha may lower LDL-C in complex, high-risk populations who need more intensive lipid lowering therapies as an optimal treatment to achieve current clinical guidelines.”
A list of Amgen-sponsored abstracts at ESC Congress 2020 can be found online and include:
Repatha data
- HAUSER-RCT evolocumab in pediatric patients with heterozygous familial hypercholesterolemia
Abstract 9097, Oral Presentation, Saturday, Aug. 29, 11:20 a.m. CEST - Achievement of ESC/EAS lipid treatment goals with evolocumab in patients with type 2 diabetes: analyses of the BANTING and BERSON trials
Abstract 8270, ePoster - Does Evolocumab use in Europe match 2019 ESC/EAS lipid guidelines? Results from the HEYMANS study
Abstract 8252, Oral Presentation, Sunday, Aug. 30 - What potential risk reduction could be achieved with evolocumab treatment? A simulation based on observational data from a cohort of users in 10 European countries
Abstract 8928, ePoster
Cardiovascular disease state and treatment studies
- Differences in lipid treatment patterns in women versus men in a large cohort of patients with atherosclerotic cardiovascular disease in Ontario, Canada
Abstract 9758/9759, Oral Presentation, Tuesday, Sept. 1 - A longitudinal evaluation of cardiovascular risk factors, treatment patterns, and outcomes in patients with documented cardiovascular disease treated with lipid lowering therapy in the United Kingdom
Abstract 8247, Abstract Only, Monday, Aug. 31 - Do European patients with peripheral arterial disease receive optimal lipid lowering therapy and achieve LDL-C goals? Results from the DA VINCI study
Abstract 8248, ePoster - What is the potential cardiovascular risk reduction associated with achieving LDL-C levels recommended in the ESC/EAS guidelines for very high-risk patients? Data from 18 European countries
Abstract 8929, ePoster - Sex differences in the rates of incident and recurrent coronary heart disease and all-cause mortality
Abstract 8884/9762, ePoster - Low-density lipoprotein cholesterol goal attainment and treatment patterns in a cohort of >143,000 patients with atherosclerotic cardiovascular disease in Ontario, Canada
Abstract 8833/9745, ePoster
Cardiovascular disease cost burden on healthcare
- Resource utilization and costs associated with achieved LDL-C levels in patients following a myocardial infarction treated with lipid-lowering therapies in Spain
Abstract 82981, ePoster - Disease burden of subsequent events among patients with atherosclerotic cardiovascular disease in Taiwan
Abstract 82915/9792, ePoster
There will also be an “Invited Talk” at the ESC/EAS Joint Session on DA VINCI Study: What have we learnt from 18 European countries on lipid management? on Sunday, Aug. 30 at 10:40 a.m. CEST.
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.4 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.
About Amgen
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.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
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 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 EU Product Information
In Europe, Repatha is approved for use in:
Hypercholesterolaemia and mixed dyslipidaemia
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.
Homozygous familial hypercholesterolaemia
Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies.
Established atherosclerotic cardiovascular disease
Repatha is indicated in adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors:
- in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or,
- alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
Posology
Primary hypercholesterolaemia and mixed dyslipidaemia in adults
The recommended dose of Repatha is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent.
Homozygous familial hypercholesterolaemia in adults and adolescents aged 12 years and over
The initial recommended dose is 420 mg once monthly. After 12 weeks of treatment, dose frequency can be up–titrated to 420 mg once every 2 weeks if a clinically meaningful response is not achieved. Patients on apheresis may initiate treatment with 420 mg every two weeks to correspond with their apheresis schedule.
Established atherosclerotic cardiovascular disease in adults
The recommended dose of Repatha is either 140 mg every two weeks or 420 mg once monthly; both doses are clinically equivalent.
Important 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.
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Special Warnings and Precautions: Renal impairment: There is limited experience with Repatha in patients with severe renal impairment (defined as eGFR < 30 mL/min/1.73 m2). 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 degrees C – 8 degrees 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 degrees C) in the original carton and must be used within 1 month.
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.
Forward-Looking Statements
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CONTACT: Amgen, Thousand Oaks
Trish Rowland, 805-447-5631 (Media)
Jessica Akopyan, 805-447-0974 (Media)
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References
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1 The FH Foundation. Heterozygous vs Homozygous FH. https://thefhfoundation.org/heterozygous-vs-homozygous-fh. Accessed August 2020. |
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2 National Human Genome Research Institute. Learning About Familial Hypercholesterolemia. http://www.genome.gov/25520184. Accessed July 2020. |
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3 McGowan MP, et al. J Am Heart Assoc. 2019;8:e013225. |
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4 World Health Organization. Cardiovascular diseases (CVDs) fact sheet. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed July 2020. |
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SOURCE Amgen
