What Is Evolocumab?
Evolocumab is an FDA-approved medication primarily used for lowering low-density lipoprotein (LDL) cholesterol, often referred to as "bad cholesterol." It belongs to a class of drugs known as PCSK9 inhibitors. Evolocumab works by binding to and blocking the function of a protein called PCSK9. This protein naturally reduces the liver's ability to remove LDL cholesterol from the blood. By inhibiting PCSK9, evolocumab effectively increases the liver's capacity to clear LDL cholesterol, leading to reduced levels in the bloodstream.
Beyond its established role in cholesterol management, Evolocumab is currently under investigation in numerous clinical trials for a variety of other conditions. These include different types of hypercholesterolemia, hyperlipidemia, and atherosclerotic cardiovascular disease. Researchers are also studying its potential benefits in acute coronary syndrome, coronary artery disease, and dyslipidemia. Further investigational uses extend to conditions such as advanced lung cancer, severe infection, and coronary allograft vasculopathy, exploring its broader therapeutic applications.
Uses and Conditions Under Study
Evolocumab is extensively studied for its impact on lipid disorders, which involve abnormal levels of fats in the blood. Conditions like Hypercholesterolemia (13 trials), Hyperlipidemia (11 trials), Dyslipidemia (5 trials), Mixed Dyslipidemia (5 trials), Primary Hypercholesterolemia (3 trials), and Familial Hypercholesterolemia (3 trials) are being investigated. These conditions are characterized by high levels of cholesterol or other lipids, and evolocumab's mechanism of action as a PCSK9 inhibitor helps reduce these levels, potentially lowering the risk of related health issues.
The drug is also a focus in cardiovascular diseases, where high cholesterol contributes to plaque buildup in arteries. Studies are ongoing for Atherosclerotic Cardiovascular Disease (8 trials), Acute Coronary Syndrome (7 trials), Coronary Artery Disease (7 trials), and Carotid Artery Stenosis (3 trials). In these conditions, evolocumab aims to reduce LDL cholesterol, which is a key factor in the progression of atherosclerosis and related cardiac events.
Beyond lipid and cardiovascular disorders, evolocumab is being explored for other therapeutic applications. For patients with Coronary Allograft Vasculopathy, a form of accelerated atherosclerosis in transplanted hearts, evolocumab is being studied to lower LDL levels and potentially improve outcomes. Research also includes its use in advanced lung cancer (non-small cell lung cancer), where it is being combined with standard immunotherapy drugs like nivolumab and ipilimumab. Additionally, evolocumab is under investigation for its effects in severe infection and in individuals who are HIV-positive, with studies evaluating its impact on endothelial function and inflammation biomarkers.
Dosing
Evolocumab is administered as a subcutaneous injection. Clinical trials have investigated various strengths and dosing frequencies for the treatment of cholesterol-related conditions and other disorders. The specific dosage forms studied include "Evolocumab drug substance A" and "Evolocumab drug substance B," indicating different formulations or presentations.
Several strengths of evolocumab have been explored in studies, including 70 mg, 105 mg, 140 mg, 280 mg, 350 mg, and 420 mg. These doses are typically administered at different intervals, such as every two weeks (Q2W), every four weeks (Q4W), or monthly (QM).
For example, some studies have evaluated evolocumab 140 mg administered every two weeks, or evolocumab 420 mg administered monthly. Other investigational regimens include evolocumab 280 mg every four weeks or evolocumab 350 mg every four weeks. The optimal strength and frequency depend on the specific condition being treated and individual patient needs, as determined by clinical trial results. Information regarding specific pediatric dosing regimens is not detailed in the provided data, with studies generally focusing on adult populations or not specifying age groups.
Side Effects
In clinical trials involving over 22,000 patients taking Evolocumab, the most frequently reported side effects included:
- Hypertension (high blood pressure) was reported in 8.3% of patients taking Evolocumab, compared to 8.9% of patients on placebo.
- Nasopharyngitis (common cold) occurred in 7.8% of patients taking Evolocumab, compared to 7.4% on placebo.
- Diabetes mellitus was observed in 7.4% of patients taking Evolocumab, versus 7.3% on placebo.
- Bronchitis affected 5.5% of patients taking Evolocumab, compared to 5.4% on placebo.
- Influenza (flu) was reported in 5.3% of patients taking Evolocumab, compared to 4.5% on placebo.
- Upper respiratory tract infection occurred in 5.2% of patients taking Evolocumab, which was the same rate as those on placebo (5.2%).
- Back pain was experienced by 4.9% of patients taking Evolocumab, compared to 4.6% on placebo.
- Arthralgia (joint pain) was reported in 4.6% of patients taking Evolocumab, compared to 5.0% on placebo.
Clinical Trial Results
NCT01133522: Study in Adults with Hyperlipidemia on Statins
This study evaluated the safety, tolerability, and effects of Evolocumab on lipid levels. Patients receiving Evolocumab experienced significant reductions in low-density lipoprotein cholesterol (LDL-C) and PCSK9 levels. For example, patients on Evolocumab 140 mg every two weeks saw their LDL-C decrease by 69.58%, while those on 280 mg every two weeks had a 74.65% reduction. Patients with Heterozygous Familial Hypercholesterolemia (HeFH) taking Evolocumab 140 mg every two weeks experienced a 62.91% reduction in LDL-C, compared to a 4.89% reduction in the placebo group. Similarly, patients on high-dose statins who added Evolocumab 140 mg every two weeks saw a 61.82% LDL-C reduction, versus a 3.01% reduction with placebo. One patient developed anti-Evolocumab antibodies in the 140 mg every two weeks group.
NCT01375751: Reduction of LDL-C in Heterozygous Familial Hypercholesterolemia
In this study focusing on patients with HeFH, Evolocumab significantly lowered LDL-C and other cholesterol markers at Week 12. Patients receiving Evolocumab 420 mg experienced a 55.24% reduction in LDL-C, compared to a 1.12% increase in the placebo group. Non-high-density lipoprotein cholesterol (Non-HDL-C) also decreased by 50.98% with Evolocumab 420 mg, versus a 2.48% increase with placebo. Apolipoprotein B, another marker for heart disease risk, was reduced by 43.34% in the Evolocumab 420 mg group, while it increased by 2.86% in the placebo group.
NCT01375764: Study in Statin-Intolerant Subjects
This trial investigated Evolocumab in patients who could not tolerate statins. At Week 12, Evolocumab showed greater reductions in cholesterol compared to ezetimibe. Patients on Evolocumab 420 mg saw their LDL-C drop by 50.70%, while those on ezetimibe experienced a 14.76% reduction. When Evolocumab was combined with ezetimibe, LDL-C was reduced by 62.98%, compared to a 15.70% reduction with ezetimibe alone. Similar trends were observed for Non-HDL-C and Apolipoprotein B, with Evolocumab showing superior reductions.
NCT01375777: Study in Adults Not on Lipid-Lowering Therapy
In patients not currently taking cholesterol-lowering medication, Evolocumab demonstrated significant reductions in LDL-C at Week 12. For example, Evolocumab 140 mg every two weeks reduced LDL-C by 50.93%, compared to a 14.26% reduction with ezetimibe and a 3.71% reduction with placebo. Non-HDL-C was lowered by 48.04% with Evolocumab 140 mg every two weeks, versus 15.53% with ezetimibe. Apolipoprotein B also decreased by 44.52% with Evolocumab 140 mg every two weeks, compared to 11.17% with ezetimibe.
NCT01380730: LAPLACE-TIMI 57 with Statin Therapy
This study examined Evolocumab when added to stable statin therapy. At Week 12, patients receiving Evolocumab 140 mg every two weeks experienced a 63.34% reduction in LDL-C, while the placebo group saw a 2.76% increase. Non-HDL-C was reduced by 59.19% with Evolocumab 140 mg every two weeks, compared to a 2.21% increase with placebo. Apolipoprotein B decreased by 50.59% in the Evolocumab 140 mg every two weeks group, versus a 5.86% increase in the placebo group.
Currently Recruiting Trials
Researchers are actively seeking participants for several clinical trials involving Evolocumab, a medication designed to lower cholesterol. These studies aim to explore new uses for the drug, compare different formulations, and understand its effects in various patient populations.
One Phase 1 study, sponsored by Amgen, is comparing two Evolocumab drug products to see how they are absorbed by the body. This trial, NCT07422285, is recruiting up to 400 healthy participants.
Another Phase 2 trial, NCT06700720, is evaluating the efficacy and safety of an intravenously administered drug, YN001, in patients with coronary atherosclerosis in Australia. This study, sponsored by Beijing Inno Medicine Co., Ltd., plans to enroll 24 participants.
For individuals with dyslipidemias, NewAmsterdam Pharma is sponsoring a Phase 2 trial, NCT06496243, to assess the impact of obicetrapib alone and in combination with Repatha (Evolocumab) on Lp(a) levels. This study is targeting 69 participants.
Several studies are focusing on cardiovascular conditions. The General Hospital of Shenyang Military Region is conducting a trial, NCT07388420, investigating Evolocumab as an add-on to conventional lipid-lowering therapy for hypertriglyceridemia-induced acute pancreatitis, with an enrollment target of 40 participants. Beijing Luhe Hospital is sponsoring a trial, NCT06364124, to examine the effects of PCSK-9 inhibitor treatment, including Evolocumab, prior to primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI), aiming for 84 participants.
The Henan Institute of Cardiovascular Epidemiology is leading a Phase 4 study, NCT05613426, to determine if very early and rapid cholesterol lowering with Evolocumab can improve left ventricular remodeling in patients with anterior STEMI undergoing primary PCI, with an enrollment goal of 330 participants. Brigham and Women's Hospital is sponsoring a Phase 4 pilot study, NCT05152888, to evaluate the impact of PCSK-9 inhibition on coronary blood flow in 50 patients with stable coronary artery disease.
NYU Langone Health is conducting a Phase 4 study, NCT05641753, on cholesterol lowering and residual risk in 125 patients with Type 1 Diabetes. Additionally, the Federico II University is sponsoring a large study, NCT05430828, to evaluate the adherence, persistence, and efficacy of PCSK9 inhibitors in a real-life Italian population of 5000 patients with hypercholesterolemia. Novartis Pharmaceuticals is also sponsoring a study, NCT06858332, in Russia to understand the distribution of Lipoprotein(a) levels among 2382 patients with atherosclerotic cardiovascular diseases and its connection to cardiovascular risk.
Where to Participate
Clinical trials for Evolocumab are currently recruiting across various locations, offering opportunities for patients in different regions to participate in research. There are 11 sites actively enrolling participants across 8 cities in 8 states within the United States, as well as international sites in Australia, Russia, and Italy.
The top recruiting locations in the United States include:
- New York, New York
- Boston, Massachusetts
- Springfield, Missouri
- Columbus, Ohio
- Philadelphia, Pennsylvania
- Dallas, Texas
- Daytona Beach, Florida
- Madison, Wisconsin
Eligibility for these studies generally includes individuals between 18 and 99 years of age, regardless of gender. Some trials are specifically designed for healthy volunteers, while others focus on patients with particular medical conditions. Children are not eligible to participate in these specific recruiting trials.
Development Timeline
The journey of Evolocumab began with its first clinical trial on May 31, 2010, marking the start of extensive research into its potential. Since then, a robust development program has unfolded, with the latest trial initiated on April 22, 2026. Over this period, a total of 125 clinical trials have been conducted or are ongoing, involving an impressive 306,225 participants.
The primary driving force behind Evolocumab's development has been Amgen, sponsoring 43 of these trials. Other institutions and pharmaceutical companies have also contributed to the research, exploring various aspects of the drug's effects.
Initially, the research explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly expanded to address a wide range of cardiovascular and metabolic conditions, reflecting the drug's mechanism of action in lowering cholesterol. The pipeline broadened significantly to include conditions like Atherosclerotic Cardiovascular Disease, Acute Coronary Syndrome, Coronary Artery Disease, Dyslipidemia, Familial Hypercholesterolemia, ST-elevation Myocardial Infarction (STEMI), and Type 1 and Type 2 Diabetes.
The development program has progressed through all phases of clinical research, with a significant number of studies in advanced stages: 38 trials in Phase 4, 37 in Phase 3, and 21 in Phase 2. This comprehensive approach demonstrates a commitment to thoroughly understanding Evolocumab's efficacy, safety, and long-term benefits across a broad spectrum of patients at risk for cardiovascular events.