What Is Bempedoic acid?
Bempedoic acid is a medication being extensively studied as a lipid-lowering agent, primarily for managing high cholesterol levels. It is investigated for conditions such as hypercholesterolemia and mixed dyslipidemia, which are characterized by elevated lipids in the blood. While the specific mechanism of action for bempedoic acid is not detailed in the provided trial descriptions, it is understood to help reduce cholesterol. This medication is explored both as a standalone therapy and in combination with other cholesterol-reducing agents, such as statins or ezetimibe, to help patients achieve target cholesterol levels. Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the risk of cardiovascular disease, a leading cause of death worldwide. Bempedoic acid has been the subject of 43 clinical trials involving a total of 33,928 participants, with the first trial starting in 2016. These studies aim to assess its effectiveness and safety in reducing cholesterol and potentially lowering the risk of cardiovascular diseases.
Uses and Conditions Under Study
Bempedoic acid is primarily studied for its effects on lipid disorders and cardiovascular health. The most common conditions under investigation include:
- High Cholesterol and Lipid Disorders: Bempedoic acid is being studied in 28 trials for various forms of high cholesterol, including hypercholesterolemia, mixed dyslipidemia, hypercholesterolaemia, hyperlipidemias, and hyper-low-density lipoprotein (LDL) cholesterolemia. These conditions involve elevated levels of fats in the blood, which can contribute to serious health problems. The medication aims to lower these lipid levels, particularly LDL-C, to improve patient outcomes.
- Cardiovascular Diseases: The drug is also being investigated in 10 trials for its potential to manage and prevent cardiovascular diseases, atherosclerotic cardiovascular disease, and atherosclerosis. By reducing cholesterol, bempedoic acid may help to slow the progression of plaque buildup in arteries and reduce the risk of heart attacks and strokes.
- Statin Adverse Reaction: In 4 trials, bempedoic acid is being studied in individuals who experience adverse reactions to statins, which are common first-line treatments for high cholesterol. For these patients, bempedoic acid may offer an alternative or complementary treatment option to help manage their cholesterol levels when statins are not well-tolerated.
- Healthy Subjects: Bempedoic acid is also studied in 4 trials involving healthy subjects. These studies typically focus on understanding how the drug is absorbed, distributed, metabolized, and excreted by the body, as well as assessing its overall safety profile in individuals without specific health conditions.
Dosing
Bempedoic acid has been studied in various dosage forms and strengths, typically administered orally once daily. The most commonly investigated strength is 180 mg. It is available as film-coated tablets, including the brand name Nilemdo®. In many trials, bempedoic acid is studied as a standalone medication, or as part of a fixed-dose combination (FDC) product with ezetimibe.
Specific dosage forms and combinations studied include:
- Over-encapsulated bempedoic acid 180 mg taken orally once daily.
- Fixed-dose combinations (FDC) of bempedoic acid (BA) and ezetimibe (EZE), such as BA 180 mg + EZE 10 mg.
- Bempedoic acid film-coated tablets.
- Earlier investigational strengths, such as ETC-1002 in 60 mg, 120 mg, and 180 mg doses.
These various forms and strengths allow for flexible treatment approaches, often tailored to a patient's specific cholesterol-lowering needs and tolerance to other medications. All mentioned dosages are for adult use, as no specific pediatric doses were detailed in the provided trial information.
Side Effects
In clinical trials, the most common side effect reported with Bempedoic acid was hyperuricaemia (high levels of uric acid in the blood). This occurred in 10.3% of patients taking Bempedoic acid across 3 trials (n=7664), compared to 5.5% of patients on placebo.
Other side effects that were reported more frequently in patients taking Bempedoic acid compared to placebo included:
- Increased blood uric acid: 5.4% of patients on Bempedoic acid vs 2.6% on placebo (3 trials, n=7664)
- Upper respiratory tract infection: 4.3% of patients on Bempedoic acid vs 3.5% on placebo (3 trials, n=3188)
Some common events occurred at similar or lower rates in patients taking Bempedoic acid compared to placebo:
- Hypertension (high blood pressure): 9.6% of patients on Bempedoic acid vs 11.0% on placebo (4 trials, n=8083)
- Arthralgia (joint pain): 6.6% of patients on Bempedoic acid vs 7.5% on placebo (9 trials, n=10775)
- Myalgia (muscle pain): 5.2% of patients on Bempedoic acid vs 6.5% on placebo (7 trials, n=8448)
Clinical Trial Results
Clinical trials have evaluated Bempedoic acid for its ability to lower cholesterol and reduce cardiovascular events.
Cardiovascular Event Reduction
In a large study (NCT02993406) involving approximately 13,970 participants at high risk for cardiovascular disease who were statin intolerant, Bempedoic acid significantly reduced the risk of major cardiovascular events.
- The occurrence of a four-component Major Adverse Cardiovascular Event (MACE), which includes cardiovascular death, non-fatal myocardial infarction (heart attack), non-fatal stroke, or coronary revascularization, was observed in 11.7% of patients taking Bempedoic acid compared to 13.3% on placebo.
- The risk of myocardial infarction (heart attack) was reduced, occurring in 3.7% of patients on Bempedoic acid vs 4.8% on placebo.
- The need for coronary revascularization (procedures to improve blood flow to the heart) was also lower, affecting 6.2% of patients on Bempedoic acid compared to 7.6% on placebo.
- The risk of stroke was 1.9% for patients on Bempedoic acid compared to 2.3% for placebo.
- There was no significant difference in all-cause mortality (6.2% vs 6.0%) or cardiovascular death (3.8% vs 3.7%) between the Bempedoic acid and placebo groups.
LDL-C and hsCRP Reduction in Statin-Intolerant Patients
A study (NCT02988115) in patients with hyperlipidemia and statin intolerance showed that Bempedoic acid effectively lowered LDL-C (bad cholesterol) and hsCRP (a marker of inflammation).
- At Week 12, patients taking Bempedoic acid experienced an average LDL-C reduction of 22.6%, compared to a 1.2% reduction in the placebo group.
- Absolute LDL-C levels decreased by an average of 37.0 mg/dL at Week 12 and 39.3 mg/dL at Week 24 with Bempedoic acid, while placebo showed minimal changes (3.1 mg/dL and 5.1 mg/dL reductions, respectively).
- High-sensitivity C-reactive protein (hsCRP) levels were reduced by 25.4% in the Bempedoic acid group at Week 12, whereas they increased by 2.7% in the placebo group.
Long-Term Efficacy
A long-term study (NCT02991118) in patients with hyperlipidemia at high cardiovascular risk demonstrated sustained benefits with Bempedoic acid over 52 weeks.
- At Week 52, LDL-C was reduced by 13.2% in the Bempedoic acid group, compared to a 1.0% reduction in the placebo group.
- HsCRP levels were reduced by 16.7% at Week 52 in the Bempedoic acid group, compared to a 6.3% reduction in the placebo group.
- Triglyceride levels increased by 11.0% in the Bempedoic acid group at Week 12, compared to a 6.1% increase in the placebo group.
Add-on to Ezetimibe Therapy
When added to ezetimibe therapy (NCT03001076), Bempedoic acid further reduced cholesterol and inflammation markers.
- At Week 12, LDL-C was reduced by 23.5% in the Bempedoic acid plus ezetimibe group, while it increased by 5.0% in the placebo plus ezetimibe group.
- HsCRP levels were reduced by 32.5% in the Bempedoic acid group, compared to a 2.1% increase in the placebo group.
Triplet Therapy with Atorvastatin and Ezetimibe
A study (NCT03051100) evaluating a triplet therapy of Bempedoic acid, ezetimibe, and atorvastatin showed substantial reductions in cholesterol.
- At Week 6, this triplet therapy reduced LDL-C by 63.6%, compared to a 3.1% reduction with placebo.
- HsCRP levels were reduced by 47.7% with triplet therapy, compared to a 2.7% reduction with placebo.
- 39 participants in the triplet therapy group achieved at least a 50% reduction in LDL-C from baseline, while no participants in the placebo group reached this goal.
Currently Recruiting Trials
Bempedoic acid is currently being investigated in several clinical trials, exploring its potential benefits for various conditions, primarily focusing on cholesterol management and related cardiovascular health. These studies aim to gather more information on its efficacy, safety, and real-world use.
- A Phase 3 study, NCT07614958, is comparing bempedoic acid against obicetrapib in 426 adults with dyslipidemia or hypercholesterolemia who are at high to very high cardiovascular risk. This randomized, double-blind trial evaluates how well each treatment lowers elevated low-density lipoprotein cholesterol (LDL-C).
- For patients with hypercholesterolemia in Italy, the Federico II University is sponsoring a multicenter study, NCT07374861, enrolling 1500 participants. This "real-life" study will assess the adherence, persistence, and overall effectiveness of bempedoic acid treatment.
- Another large study, NCT06686615, sponsored by Daiichi Sankyo Europe, GmbH, is enrolling 2000 individuals with primary hypercholesterolemia or mixed dyslipidemia. It aims to collect real-world data on the use, effectiveness, and safety of bempedoic acid when combined with ezetimibe and either rosuvastatin or atorvastatin.
- Gan & Lee Pharmaceuticals is conducting a Phase 3 trial, NCT06780410, with 240 participants to evaluate the efficacy, tolerability, and safety of Bempedoic Acid Tablets in patients whose hyperlipidemia is not adequately controlled by statins.
- The effect of bempedoic acid on liver fat is being explored in a study, NCT06035874, involving 100 individuals with nonalcoholic fatty liver disease (NAFLD) and Type 2 Diabetes. This trial, sponsored by Medanta, The Medicity, India, investigates its potential role in these interconnected conditions.
- A Phase 2, randomized, placebo-controlled study called the CLEAR HIV Trial (NCT05488431) is enrolling 121 HIV-infected individuals aged 40 or older with cardiovascular disease or risk factors. This study aims to understand bempedoic acid's effect on arterial inflammation, lipids, and immune activation.
- Finally, a pregnancy surveillance program, NCT05103254, is underway with 20 participants to monitor the use of bempedoic acid in pregnant individuals with hyperlipidemias.
Where to Participate
If you are interested in participating in a clinical trial for bempedoic acid, studies are currently recruiting across various locations. While many trials are global, specific sites are actively seeking participants in the United States.
Current recruiting locations include:
- Los Angeles, California
- San Francisco, California
- Morrisville, North Carolina
- Houston, Texas
General eligibility criteria for these studies typically require participants to be between 18 and 40 years of age. All genders are welcome to participate, but these trials are not designed for healthy volunteers or children.
Development Timeline
The journey of bempedoic acid in clinical development began on December 9, 2016, with the initiation of its first clinical trial. Since then, the drug has undergone extensive investigation, with a total of 43 trials conducted or planned, enrolling over 33,928 participants.
Esperion Therapeutics, Inc. has been a primary driver of bempedoic acid's development, sponsoring 12 trials, with significant contributions from other pharmaceutical companies like Daiichi Sankyo. The development pipeline has seen progression through all clinical phases, including Phase 1, Phase 2, and a substantial number of Phase 3 studies, with some trials also designated as Phase 4 or "Not Specified" for real-world data collection.
Initially, the focus of bempedoic acid's research included conditions like IBS-C and hyperphosphatemia. Over time, the scope broadened significantly to address a wide range of cardiovascular and metabolic conditions. The drug's development expanded to target conditions such as atherosclerotic cardiovascular disease, various forms of hypercholesterolemia and dyslipidemias, and even specific populations like HIV-infected individuals and those with nonalcoholic fatty liver disease or Type 2 Diabetes. The latest planned trial is set to conclude by May 29, 2026, indicating ongoing commitment to understanding its full therapeutic potential.