Amgen Announces Positive Data From Phase 3B Study Of Repatha® (Evolocumab) In Pediatric Patients With Heterozygous Familial Hypercholesterolemia At ESC Congress 2020
Amgen announced positive results from the HAUSER-RCT Phase 3b study for Repatha® (evolocumab) in pediatric patients aged 10-17 with heterozygous familial hypercholesterolemia (HeFH). The study demonstrated a significant 38.3% reduction in LDL-C levels compared to placebo, meeting its primary endpoint. It was presented at ESC 2020 and published in The New England Journal of Medicine. No new safety risks were noted, with adverse events being generally mild. The study emphasizes Repatha's potential as a safe and effective option for managing high cholesterol in children.
- 38.3% mean reduction in LDL-C levels in pediatric patients with HeFH.
- No new safety risks identified, indicating a favorable safety profile.
- Strengthens evidence base for Repatha, enhancing its value in pediatric cholesterol management.
- None.
THOUSAND OAKS, Calif., Aug. 29, 2020 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced positive data from the HAUSER-RCT Phase 3b study evaluating the safety and efficacy of Repatha® (evolocumab) in pediatric patients, 10-17 years of age, with heterozygous familial hypercholesterolemia (HeFH). The study showed that Repatha, in combination with statins and other lipid-lowering therapies, significantly reduced low-density lipoprotein cholesterol (LDL-C) compared to placebo. These data are being presented during an oral presentation at ESC 2020 – The Digital Experience, organized by the European Society of Cardiology, Aug. 29–Sept. 1 and simultaneously published in The New England Journal of Medicine.
HeFH is an inherited, genetic condition with a prevalence of one in 250 people worldwide.1 High levels of low-density lipoprotein cholesterol (LDL-C) starting at birth accelerate the development of atherosclerotic cardiovascular disease, leading to an overall increased risk of cardiovascular events, including heart attack and other vascular conditions, and decreasing the age at which such events occur.2 Children with FH can be normal weight, have a good diet, exercise enough, and still have high LDL-C.2,3 The risk of heart disease in people with FH is about 20 times greater versus the general population.4
"Pediatric patients with FH are at increased risk for cardiovascular events from a very early age, making effective management of LDL-C levels in children with HeFH so important," said Daniel Gaudet, M.D., Ph.D., from the Department of Medicine at the Université de Montréal and senior author of the Hauser-RCT study. "This study shows the potential that Repatha offers as a safe and effective treatment option in pediatric HeFH patients already on lipid-lowering therapies who need further LDL-C reduction."
Results from the randomized, double-blind 24-week study show that in pediatric patients with HeFH, monthly treatment with Repatha reduced LDL-C by mean
"Amgen is dedicated to advancing the care and improving the lives of patients with cardiovascular disease. This includes investing in clinical trials and real-world evidence studies to better understand the safety and efficacy of Repatha across various patient populations and those most in need," said David M. Reese, M.D., executive vice president of research and development at Amgen. "This study increases our overall evidence base for Repatha and provides us with a better understanding of cholesterol management in children with genetically high LDL-C, bringing us one step closer to another treatment option for this historically underdiagnosed and undertreated condition."
"As a parent, it can be hard to understand that your child who looks healthy, eats well and is active, is suffering from an invisible condition that can cause an early heart attack or stroke," said Katherine Wilemon, Founder and CEO of The FH Foundation. "The good news is that with early and ongoing treatment, people with FH can greatly reduce cardiovascular risk by lowering their LDL-cholesterol. This trial data gives us hope for new, safe and effective therapies for children living with familial hypercholesteremia."
About Familial Hypercholesterolemia
Elevated LDL-C is an abnormality of cholesterol and/or fats in the blood.6,7 FH is an inherited condition that causes high levels of LDL-C at an early age.8 It is estimated that 1 million people in the U.S. have FH (heterozygous and homozygous forms), yet less than
About HAUSER-RCT Study Design
HAUSER-RCT was a Phase 3b, multicenter, randomized (2:1), double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of 24 weeks of monthly subcutaneous injections of Repatha® (evolocumab) 420 mg (n = 104) versus placebo (n = 53) in patients 10 to 17 years of age with heterozygous familial hypercholesteremia, or HeFH. Randomization was stratified by LDL-C (<4.1 versus ≥4.1 mmol/L) and age (<14 versus ≥14 years of age) at screening. Key eligibility criteria included fasting LDL-C ≥3.4 mmol/L on a low-fat diet and maximum LLT for ≥4 weeks before screening. The primary endpoint was percent change in LDL-C from baseline to week 24; secondary endpoints included mean percent change in LDL-C from baseline to week 22 and 24, change in LDL-C from baseline to week 24, percent changes from baseline to week 24 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/apolipoprotein A1 (ApoA1) ratio. Further safety evaluations included Tanner staging, hormone levels, carotid intimal medial thickness, and computer-based cognitive assessments.
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.11 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 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 (>
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in
Allergic reactions occurred in
The most common adverse reactions in the Cardiovascular Outcomes Trial (>
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was
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.
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.
Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company, including Adaptive Biotechnologies (including statements regarding such collaboration's, or our own, ability to discover and develop fully-human neutralizing antibodies targeting SARS-CoV-2 to potentially prevent or treat COVID-19), BeiGene, Ltd., or the Otezla® (apremilast) acquisition, including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion, as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems such as the ongoing COVID-19 pandemic on our business, outcomes, progress, or effects relating to studies of Otezla as a potential treatment for COVID-19, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
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References
1 The FH Foundation. Heterozygous vs Homozygous FH. https://thefhfoundation.org/heterozygous-vs-homozygous-fh. Accessed August 2020.
2 McGowan MP, et al. JAMA. 2019;8:e013225.
3 The FH Foundation. Children with FH. https://thefhfoundation.org/familial-hypercholesterolemia/children-with-fh. Accessed August 2020.
4 FH Foundation. What are the Risks with FH? https://thefhfoundation.org/familial-hypercholesterolemia/what-are-the-risks-with-fh. Accessed August 2020.
5 Santos RD, et al. Evolocumab Treatment in Pediatric Patients with Heterozygous Familial Hypercholesterolemia: Primary Results of HAUSER-RCT, a Phase 3B, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Presented at ESC Congress 2020. Abstract 9097.
6 World Health Organization. Quantifying Selected Major Risks to Health. In: The World Health Report 2002 - Reducing Risks, Promoting Healthy Life. Geneva. 2002:49-97.
7 Merck Manuals website. http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html. Accessed August 2020.
8 National Human Genome Research Institute. Learning About Familial Hypercholesterolemia. http://www.genome.gov/25520184. Accessed August 2020.
9 Nordestgaard BG, et al. Eur Heart J. 2013;34:3478–3490.
10 Centers for Disease Control and Prevention. Finding Family Members with Familial Hypercholesterolemia. 2020. https://www.cdc.gov/genomics/disease/fh/finding_FH.htm#:~:text=Although%20more%20than%20one%20million,%2C%20genetic%20testing%2C%20or%20both. Accessed August 2020.
11 World Health Organization. Cardiovascular diseases (CVDs). http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed August 2020.
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