FDA Expands Evolocumab to Treat Adults at Increased Risk for Major Adverse Cardiovascular Events

The FDA has broadened the approval of evolocumab (Repatha; Amgen), a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), to include adults at increased risk for major adverse cardiovascular events (MACE) caused by uncontrolled low-density lipoprotein cholesterol (LDL-C). The recent update no longer requires a patient to have a prior diagnosis of cardiovascular disease.¹

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The drug 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.²

LDL-C and Cardiovascular Disease

High levels of LDL-C, or bad cholesterol, can significantly increase the risk of heart attacks and strokes. Over time, too much LDL-C causes plaque to build up in the arteries, which can block blood flow, leading to coronary artery disease, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. However, unlike unchangeable risk factors like age or genetics, LDL-C is a modifiable risk factor that can be lowered through lifestyle changes and treatment that can reduce cardiovascular risk. Lifestyle changes that health care providers recommend include eating heart-healthy foods, avoiding tobacco use, maintaining a weight that’s healthy, lowering stress, and taking medication.^3,4

"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 news release.¹

Evolocumab’s Role for MACE

By binding to PCSK9, evolocumab prevents it from breaking down LDL receptors on the surface of liver cells. This action increases the number of available LDL receptors, which helps clear more LDL cholesterol from the blood, causing the LDL-C levels to lower.¹

The study authors noted that the safety and effectiveness of evolocumab have been supported by 15 years of research across 50 clinical trials that included more than 57,000 patients. This includes various phase 3 trials that added evolocumab to background lipid-lowering therapy that included statins, resulting in significant reductions in LDL-C levels. Additionally, patients with ASCVD and HeFH demonstrated a reduced LDL-C by about 54% to 77% compared with placebo, leading to its initial approval.²

In a cardiovascular outcomes trial, the most common adverse effects (AEs) seen in more than 5% of patients taking evolocumab were diabetes, nasopharyngitis, and upper respiratory tract infections. Additionally, these AEs were more frequently observed in this treatment group than in those receiving placebo. Among individuals who did not have diabetes at the start of the study, new cases of the condition occurred in 8.1% of the group treated with evolocumab compared with 7.7% in the placebo group.¹

The expansion of evolocumab is indicated to reduce the risk of MACE events, including cardiovascular death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization among adults that are at an increased risk of these events.¹

"This label update highlights the real-world need for additional treatment options for at-risk patients. [Evolocumab] is an effective therapy for reducing LDL-C, particularly in patients whose disease remains uncontrolled with statins or who cannot tolerate them,” Gordon said in the news release.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://www.amgen.com/newsroom/press-releases/2025/08/repatha-now-indicated-for-adults-at-increased-risk-for-major-adverse-cardiovascular-events-due-to-uncontrolled-ldl-c

2. 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

3. Understanding Cardiovascular Risk: The Role of LDL-C, Comorbidities and Early Intervention. Amgen. November 13, 2024. Accessed August 25, 2025. https://www.amgen.com/stories/2024/11/understanding-cardiovascular-risk---the-role-of-ldl-c-comorbidities-and-early-intervention#:~:text=Over%20time%2C%20high%20levels%20of,the%20risk%20of%20CV%20events.

4. LDL Cholesterol. Cleveland Clinic. News release. Updated December 23, 2024. Accessed August 25, 2025. https://my.clevelandclinic.org/health/articles/24391-ldl-cholesterol