Repatha is the Only PCSK9 Inhibitor to Significantly Reduce the Risk of First CV Events in High-Risk Primary Prevention

VESALIUS-CV Subgroup Findings Reinforce Benefit of Earlier Initiation of Repatha in High-Risk Patients, with Median 44 mg/dL LDL-C Achieved

THOUSAND OAKS, Calif., March 28, 2026 /PRNewswire/ -- Amgen (NASDAQ:AMGN) announced today that Repatha^®(evolocumab), when added to statins or other low-density lipoprotein cholesterol (LDL-C)-lowering treatments, reduced the risk of first major adverse cardiovascular (CV) events (MACE) in high-risk primary prevention patients without known significant atherosclerosis (buildup of plaque in the arteries) and with diabetes. The findings were presented in a late-breaking session at the American College of Cardiology (ACC) 75th Annual Scientific Session and simultaneously published in the Journal of the American Medical Association.

The results are from a new subgroup analysis of 3,655 patients at increased risk of CV events without known significant atherosclerosis (all of whom had diabetes) followed for a median of 4.8 years from the Phase 3 VESALIUS-CV clinical trial. Results showed Repatha reduced the risk of the composite primary endpoint of coronary heart disease (CHD) death, myocardial infarction or ischemic stroke (3‑P MACE) by 31% compared with placebo. Repatha also reduced the risk of a dual composite primary endpoint that included ischemia‑driven revascularization (4‑P MACE) by 31%. The median achieved LDL-C was 44 mg/dL at 96 weeks in the Repatha added to optimized lipid-lowering therapy arm compared to 105 mg/dL in the placebo plus optimized lipid-lowering therapy arm (548 patients in the subgroup were part of a lipid sub-study).

"The evidence is unequivocal: Intensive LDL-C lowering with Repatha significantly reduces the risk of major CV events for high-risk patients," said Jay Bradner, M.D., executive vice president of Research and Development at Amgen. "The new ACC/AHA Multisociety Guideline on the Management of Dyslipidemia reinforces the importance of earlier, more intensive lowering of LDL-C to prevent CV events. VESALIUS-CV builds on this, showing that in high-risk patients without prior heart attack or stroke, lowering LDL-C beyond what is typically achieved today can meaningfully reduce risk before ASCVD takes hold. These data also show the benefit of lowering LDL-C below 45 mg/dL with Repatha, a level that may not be achieved with statins or ezetimibe alone. Now is the time to treat earlier and help all appropriate patients reach lower LDL-C goals."

Across secondary endpoints, Repatha demonstrated consistent benefit, including the following composite endpoints: heart attack, ischemic stroke or any ischemia-driven revascularization; CHD death, heart attack or revascularization; CV death, heart attack or ischemic stroke. Among individual secondary endpoints, Repatha showed numerical reductions in the risk of heart attack by 31%, ischemia-driven revascularization by 34% and ischemic stroke by 33%. Repatha demonstrated numerical trends for reduced mortality rates, including CV death (32% relative risk reduction), CHD death (27% relative risk reduction) and all‑cause death (24% relative risk reduction).

"This analysis clearly demonstrates that the CV benefit of evolocumab in the VESALIUS-CV study includes those who had no known ASCVD, or significant plaque buildup in the arteries," said Nicholas Marston, M.D., M.P.H., assistant professor of medicine, member of the TIMI Study Group and cardiologist at Brigham and Women's Hospital and Harvard Medical School. "Lowering LDL-C earlier with more intensive therapy in high-risk primary prevention patients, before plaque becomes advanced, can prevent the clinical onset of heart disease. These findings confirm the substantial risk reduction that can be achieved by treating more proactively with evolocumab rather than waiting for the development of significant atherosclerosis or a CV event to then intensify lipid-lowering therapy."

For more information on Amgen abstracts and presentation times at the ACC 75th Annual Scientific Session, see below.

Evolocumab for the Reduction of First Major Cardiovascular Events in Patients without Significant Atherosclerosis: Results from VESALIUS-CV

LBS.105, Saturday, March 28 from 4:00 - 4:10 p.m. CST
LDL-C Lowering and Associated Risk Reduction of Myocardial Infarction and Stroke-Related Hospitalizations in Patients with ASCVD and Diabetes

Abstract #1165-11, Monday, March 30 from 10:18 - 10:25 a.m. CST

Cardiovascular disease (CVD) is the leading cause of death worldwide, and most CV events occur in people without a prior history of heart attack or stroke.¹ High LDL-C is one of the most modifiable risk factors for heart attack and stroke, and prolonged exposure to elevated LDL‑C increases CV risk over time, making earlier and more intensive LDL‑C lowering critical to reducing the risk of a first CV event.^2,3,4

Repatha was first approved in 2015 and has since been used by more than 8 million patients globally.^5,6In August 2025, the U.S. Food and Drug Administration broadened the approved use of Repatha to include adults at increased risk for major adverse CV events due to uncontrolled LDL-C.

About the VESALIUS-CV Trial

VESALIUS-CV is a Phase 3, double-blind, randomized, placebo-controlled, global clinical trial designed to evaluate the impact of LDL-C lowering with evolocumab on MACE in adults at high CV risk without prior heart attack or stroke. Results were published in the New England Journal of Medicine in November 2025. Repatha demonstrated a 25% relative reduction in the risk of a composite of coronary heart disease (CHD) death, heart attack or ischemic stroke (3-P MACE), and 19% reduction in a broader composite that also included any ischemia-driven arterial revascularization (4-P MACE). Repatha also reduced the risk of heart attack by 36%.

VESALIUS-CV enrolled more than 12,000 patients with known ASCVD or high-risk diabetes, who had no history of heart attack or stroke, an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with highest tolerated dose of statin and/or ezetimibe. The median baseline LDL-C was 122 mg/dL (IQR, 104-149 mg/dL) on local lab testing. Participants were randomized to receive Repatha or placebo in addition to optimized lipid-lowering therapy and were followed for a median of approximately 4.6 years.

Amgen's Commitment to Cardiovascular Innovation

Cardiovascular disease (CVD) remains a major global health threat, linked to multiple interrelated risk factors like high LDL-C, Lp(a), obesity, diabetes and hypertension.^7,8 These risks often coexist and require a comprehensive approach to prevention and care. Amgen is taking bold action, building on decades of leadership in CVD through LDL-C management to advance additional innovative, investigational treatments in the pipeline targeting common drivers of CVD. By combining scientific innovation with strategic partnerships to drive earlier testing, better care and broader access, Amgen's efforts reflect a sustained commitment to advancing both the science and the system of CV care.

About Repatha

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 one of the most extensively studied PCSK9 inhibitors, with clinical and real-world evidence across diverse populations and CV risk profiles.⁸ The clinical benefits and safety of Repatha have been studied for 15 years in 51 clinical trials with over 57,000 patients.⁹ Repatha is the only PCSK9 inhibitor to demonstrate a significant reduction of cardiovascular events as both high-risk primary and secondary prevention. Repatha has been prescribed to over 8 million patients globally and is approved in 74 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union.⁹ Applications in other countries are pending.

INDICATIONS

Repatha^® is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor indicated:

To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events.
As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in:

adults with hypercholesterolemia.
adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).

The safety and effectiveness of Repatha^®have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hypercholesterolemia. For full prescribing information, visit www.Repatha.com.

IMPORTANT SAFETY INFORMATION

Contraindication: Repatha^® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha^®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha^®.
Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha^®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha^®, treat according to the standard of care, and monitor until signs and symptoms resolve.
Adverse Reactions in Adults with Primary Hypercholesterolemia: The most common adverse reactions (>5% of patients treated with Repatha^® and 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. Hypersensitivity reactions occurred in 5.1% and 4.7% of Repatha^®-treated and placebo-treated patients, respectively. The most common hypersensitivity 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%).
Adverse Reactions in the FOURIER Cardiovascular Outcomes Trial: The most common adverse reactions (>5% of patients treated with Repatha^® and 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 treated with Repatha^® compared with 7.7% in patients that received placebo.
Adverse Reactions in Pediatric Patients with HeFH: The most common adverse reactions (>5% of patients treated with Repatha^® and more frequently than placebo) were: nasopharyngitis, headache, oropharyngeal pain, influenza, and upper respiratory tract infection.
Adverse Reactions in Adults and Pediatric Patients with HoFH: In a 12-week study in 49 patients, 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. In an open-label extension study in 106 patients, including 14 pediatric patients, no new adverse reactions were observed.
Immunogenicity: Repatha^® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha^®.

Please see full Prescribing Information.

About Amgen

Amgen discovers, develops, manufactures and delivers innovative medicines to fight some of the world's toughest diseases. Harnessing the best of biology and technology, Amgen reaches millions of patients with its medicines.

More than 45 years ago, Amgen helped establish the biotechnology industry at its U.S. headquarters in Thousand Oaks, California, and it remains at the cutting edge of innovation, using technology and human genetic data to push beyond what is known today. Amgen is advancing a broad and deep pipeline and portfolio of medicines to treat cancer, heart disease, inflammatory conditions, rare diseases and obesity and obesity-related conditions.

Amgen has been consistently recognized for innovation and workplace culture, including honors from Fast Company and Forbes. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average^®, and it is also part of the Nasdaq-100 Index^®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, YouTube, Facebook, TikTok and Threads.

Amgen 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 BeOne Medicines Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla^® (apremilast), our acquisitions of ChemoCentryx, Inc., Dark Blue Therapeutics, Ltd. or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), 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 on our business, outcomes, progress, 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.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.

Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions, including those resulting from geopolitical relations and government actions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our sustainability objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

CONTACT: Amgen, Thousand Oaks

Madison Howard, 773-636-4910 (media)

Elissa Snook, 609-251-1407 (media)

Casey Capparelli, 805-447-1746 (investors)

REFERENCES

Martin SS, Aday AW, Allen NB, et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee. 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation. 2025151(8)le41–e660. https://doi.org/10.1161/CIR.0000000000001303
Jurin I, et al. Outcomes of patients with normal LDL-cholesterol at admission for acute coronary syndromes: lower is not always better. J Cardiovasc Dev Dis. 2024;11(4):120. https://doi.org/10.3390/jcdd11040120
Domanski MJ, Tian X, Wu CO, et al. Time course of LDL cholesterol exposure and cardiovascular disease event risk. J Am Coll Cardiol. 2024;76(13):1507-1516.
Kalra DK, Ray KK, Bajaj A, et al. Low-density lipoprotein cholesterol lowering and risk of major adverse cardiovascular events in primary prevention trials: A meta-analysis. J Clin Lipidol. 2026.
Shapiro MD. Prolonged and Pronounced Low-Density Lipoprotein Cholesterol Lowering: The Gift That Keeps Giving. Circulation. 2022;146(15):1120-1122.
Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862.
Vasan RS, Enserro DM, Xanthakis V, Beiser AS, Seshadri S. Temporal trends in the remaining lifetime risk of cardiovascular disease among middle-aged adults across 6 decades: the Framingham Study. Circulation. 2022:145(17):1324-1338. https://doi.org/10.1161/CIRCULATIONAHA.121.057889
Tsimikas S, Marcovina S. Ancestry, lipoprotein(a), and cardiovascular risk thresholds: JACC Review Topic of the Week. JACC. 2022;80(9):934-946. https://doi.org/10.1016/j.jacc.2022.06.019 MAC: REF-99099
Data on File. Amgen, 2025.

View original content to download multimedia:https://www.prnewswire.com/news-releases/repatha-cuts-risk-of-first-major-cardiovascular-events-by-31-in-high-risk-patients-without-known-significant-atherosclerosis-302727943.html

SOURCE Amgen

REPATHA® CUTS RISK OF FIRST MAJOR CARDIOVASCULAR EVENTS BY 31% IN HIGH-RISK PATIENTS WITHOUT KNOWN SIGNIFICANT ATHEROSCLEROSIS