FDA Expands Evolocumab Indication to Adults at Risk for Major Cardiovascular Events Due to Uncontrolled LDL-C

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The US Food and Drug Administration (FDA) has broadened the indication for evolocumab (Repatha,^® Amgen), approving its use in adults at increased risk for major adverse cardiovascular events (MACE) due to uncontrolled low-density lipoprotein cholesterol (LDL-C), Amgen announced August 25, 2025. The update removes the previous requirement that patients must already have a diagnosis of cardiovascular disease.¹

According to the company's press release, the expanded indication reflects the need for additional treatment options in people who remain above LDL-C targets despite statin therapy or who are unable to tolerate statins. Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduces LDL-C by preventing PCSK9 from degrading LDL receptors, thereby increasing clearance of LDL from the blood.¹

"Far too many adults at risk of cardiovascular disease are not achieving their LDL-C goals, despite it being one of the most modifiable risk factors for a heart attack or stroke," Murdo Gordon, executive vice president of Global Commercial Operations at Amgen, said in a press release. "This label update highlights the real-world need for additional treatment options for at-risk patients. Repatha is an effective therapy for reducing LDL-C, particularly in patients whose disease remains uncontrolled with statins or who cannot tolerate them."¹

According to the US CDC, CVD has been the leading cause of death in the US since 1950. From 2009 to 2012, the age-adjusted CVD death rate decreased from 182.8 to 170.5 per 100 000, respectively, and then decreased slower in 2019 with 161.5 per 100 000 age-adjusted deaths. In 2019, the CDC reported a total of 659 041 deaths in 2019.²

High LDL-C is an established risk factor for CVD, including MACE—myocardial infarction, coronary artery disease death, or stroke. Current guidelines recommend lifestyle modifications that reduce total fat intake and dietary cholesterol, and when that is ineffective for patients, it is recommended to initiate statins. However, some patients could be intolerant to statins or experience adverse effects (AEs), including myopathy or gastrointestinal disorders.³

As part of the updated label for evolocumab, the FDA also expanded the use of the drug as a monotherapy for individuals with homozygous familial hypercholesterolemia (HoFH), a rare genetic condition characterized by markedly elevated cholesterol levels. The updated label continues to emphasize that the drug should be used alongside diet and exercise for cholesterol management.¹

Evolocumab was initially approved by the FDA in August 2015 and is indicated to lower LDL-C in adults with heterozygous familial hypercholesterolemia (HeFH) or existing clinical atherosclerotic cardiovascular disease (ASCVD) alongside diet and a statin and is used with other LDL-lowering treatments to help patients with HoFH to further reduce their LDL-C levels.⁴ It has been used by more than 5 million people worldwide and is currently approved in more than 74 countries, including the US, Canada, Japan, and across the European Union.¹

Common adverse reactions observed in clinical studies included nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions. Hypersensitivity reactions, including angioedema, have been reported. In cardiovascular outcomes trials, diabetes mellitus, nasopharyngitis, and upper respiratory tract infection were the most frequently reported adverse events.¹

References:

1. REPATHA® Now Indicated for Adults at Increased Risk for Major adverse Cardiovascular Events Due to Uncontrolled LDL-C. Amgen. News release. August 25, 2025. Accessed August 25, 2025. https://investors.amgen.com/news-releases/news-release-details/repathar-now-indicated-adults-increased-risk-major-adverse
2. CDC. Heart disease deaths. August 5, 2024. Accessed August 26, 2025. https://www.cdc.gov/nchs/hus/topics/heart-disease-deaths.htm
3. Morgan CL, Durand A, McCormack T, et al. Risk of major adverse cardiovascular events associated with elevated low-density lipoprotein cholesterol in a population with atherosclerotic cardiovascular disease with and without type 2 diabetes: a UK database analysis using the Clinical Practice Research Datalink. BMJ Open. 2023;13:e064541. doi:10.1136/bmjopen-2022-064541
4. FDA Approves Amgen's New Cholesterol-Lowering Medication Repatha™ (evolocumab). Amgen. News release. August 27, 2015. Accessed August 25, 2025. https://www.amgen.com/newsroom/press-releases/2015/08/fda-approves-amgens-new-cholesterollowering-medication-repatha-evolocumab