MUNICH--(BUSINESS WIRE)--Daiichi Sankyo Europe GMbH (hereafter, ‘Daiichi Sankyo’) today announced positive initial results from the 12-week Phase 2 bempedoic acid / ezetimibe fixed dose combination (FDC) tablet study (also known as Study 058). Bempedoic acid and its FDC tablet with ezetimibe are currently undergoing regulatory review for marketing authorisation by the European Medicines Agency (EMA) and by the United States Food and Drug Administration (FDA).
Study 058 evaluated the efficacy and safety of the bempedoic acid / ezetimibe FDC tablet compared to ezetimibe and placebo in patients with both hypercholesterolaemia and type 2 diabetes. Participants were on a background of stable diabetes medication.
The 12-week study met its primary endpoints as well as key secondary endpoints, including that the bempedoic acid / ezetimibe FDC tablet:
- Significantly lowered Low-Density Lipoprotein Cholesterol (LDL-C) by 40% compared to placebo
- Reduced high-sensitivity C-Reactive Protein (hsCRP), an important marker of inflammation associated with cardiovascular disease, by 25% (p<0.001)
- Did not result in any difference in haemoglobin A1c (HbA1c) compared to placebo
- Overall adverse events (AEs) comparable to placebo
- Had no increase in muscle-related AEs, serious adverse events (SAEs), discontinuations due to AEs or elevations in liver function tests (LFTs)
- Achieved LDL-C <70 mg/dl in 39% of patients and reduction of >50% in 41% of patients
- Resulted in consistent reductions in additional lipid parameters such as apolipoprotein B and non-High-Density Lipoprotein Cholesterol (HDL-C).
“The LDL-C lowering and hsCRP reductions seen with the bempedoic acid / ezetimibe once-daily combination oral tablet, without worsening glycaemic parameters, are very important to physicians like me who frequently manage patients with both hypercholesterolaemia and type 2 diabetes. In addition, the substantial reductions in apolipoprotein B and non-HDL-C observed in this study may be particularly important for patients with hypercholesterolaemia and type 2 diabetes,” said Dr Harold Bays, medical director and president of the Louisville Metabolic and Atherosclerosis Research Center. “Patients benefit from having more therapeutic options, especially ones that improve multiple cardiovascular disease risk factors.”
Study 058 showed no clinical differences between the bempedoic acid / ezetimibe FDC tablet, placebo and ezetimibe groups in the occurrence of:
- AEs with 43%, 37% and 30%, respectively
- SAEs with 0%, 2% and 2%, respectively
- Discontinuations due to AEs with 0%, 0% and 2%, respectively
- No elevations in LFTs (alanine aminotransferase (ALT) /alanine aminotransferase (AST) greater than three times the upper limit of normal, repeated and confirmed) were observed.
“This study highlights the potential of this once-daily tablet to treat people with increasingly common metabolic conditions, who often struggle to reach targets suggested by clinical guidelines to provide maximum protection from cardiovascular events,” said Wolfgang Zierhut, MD, Head of Antithrombotic and Cardiovascular Medical Affairs Department at Daiichi Sankyo Europe. “People living with type 2 diabetes are at increased cardiovascular risk, and as the incidence of type 2 diabetes across Europe continues to increase we need new options to help protect people trying to lower their cholesterol levels without compromising their glycaemic control.”
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Design of Phase 2 Study (1002FDC-058)
This phase 2, double-blind, parallel group, multicenter study randomised 242 patients with hypercholesterolaemia and type 2 diabetes who were being treated with stable diabetes medication and washed out of lipid modifying therapy. Patients were randomised 1:1:1 to receive bempedoic acid 180 mg / ezetimibe 10 mg FDC tablet, ezetimibe 10 mg or placebo. The co-primary objectives included assessments of LDL-C lowering of the bempedoic acid / ezetimibe FDC tablet versus ezetimibe and placebo. Among the 179 patients included in this analysis, the bempedoic acid / ezetimibe FDC tablet significantly lowered LDL-C by 40% compared to placebo (placebo-corrected difference). The secondary objectives included assessments of high-sensitivity C-reactive protein (hsCRP), haemoglobin A1c (HbA1c), non-HDL-C, total cholesterol (TC), and apolipoprotein B (apoB) after 12 weeks of treatment as well as characterising the safety and tolerability of the bempedoic acid / ezetimibe FDC tablet versus ezetimibe and placebo.
With a targeted mechanism of action, bempedoic acid is an oral, once-daily ATP Citrate Lyase (ACL) inhibitor that reduces cholesterol synthesis in the liver and thereby lowers circulating LDL-C levels.1,2 It is intended for patients with hypercholesterolaemia and/or at high risk of atherosclerotic cardiovascular disease (ASCVD) who need additional LDL-C lowering despite maximally tolerated statin therapy.
Bempedoic acid has a unique, innovative mode of action, which is complimentary to other lipid-lowering therapies, such as statins.3 Due to its liver-specific mode of action, bempedoic acid has a reduced potential to induce the muscle-related side-effects associated with statin therapy and provide additional LDL-C lowering on top of statin monotherapy in clinical trials.2
Completed Phase 2 and Phase 3 studies conducted in almost 4,800 patients, and approximately 3,100 patients treated with bempedoic acid, have demonstrated: an additional 20% LDL-C lowering (placebo-corrected) when added to moderate-to-high intensity statin background treatment; 28% LDL-C lowering (placebo-corrected) when added to no-or-low intensity statin background treatment; up to 38% (placebo-corrected) LDL-C lowering when administered as a fixed dose combination with ezetimibe in patients on maximally tolerated statin therapy.1,2,4
Bempedoic acid (180 mg) and the bempedoic acid / ezetimibe fixed dose combination tablet (180 mg/10 mg) are currently under review by the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use and the U.S. Food and Drug Administration for LDL-C lowering in patients who are not yet at their target LDL-C level. Daiichi Sankyo Europe licensed exclusive commercialisation rights to these products in the European Economic Area and Switzerland from Esperion. Approval decisions are expected during the first half of 2020.
Bempedoic Acid / Ezetimibe FDC: https://www.daiichi-sankyo.eu/media/bempedoic
About Daiichi Sankyo
Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address diversified, unmet medical needs of patients in both mature and emerging markets. With over 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for hypertension and thrombotic disorders, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology”, Daiichi Sankyo research and development is primarily focused on bringing forth novel therapies in oncology, including immuno-oncology, with additional focus on new horizon areas, such as pain management, neurodegenerative diseases, heart and kidney diseases, and other rare diseases. For more information, please visit: www.daiichisankyo.com.
1 Ray KK, et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med. 2019;380:1022-32.
2 Ballantyne CM, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis.2018;277:195-203.
3 Laufs U, et al. Efficacy and Safety of Bempedoic Acid in Patients with Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc. 2019;8(7):e011662.
4 Ballantyne, CM, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2019; doi 10.1177/2047487319864671.