DAIICHI-SANKYO

Daiichi Sankyo Europe GmbH (hereafter, ‘Daiichi Sankyo’) today announced the publication of results from the Phase 3 CLEAR Wisdom trial in the Journal of the American Medical Association (JAMA) .¹ Bempedoic acid is currently undergoing review for marketing authorisation by the European Medicines Agency (EMA) and by the United States Food and Drug Administration (FDA).

CLEAR Wisdom, a Phase 3, double-blind, randomised trial, evaluated the efficacy, long-term safety and tolerability of bempedoic acid 180 mg versus placebo in 779 patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolaemia (HeFH) inadequately controlled with current lipid-modifying therapies, added on to maximally-tolerated statin therapy, which may mean no statin at all.¹

The JAMA publication includes results for the primary efficacy endpoint of low-density lipoprotein cholesterol (LDL-C) lowering at 12 weeks and key secondary endpoints of safety and tolerability over 52 weeks. The publication reports that bempedoic acid:¹

• significantly lowered LDL-C by 17% on background maximally-tolerated statin therapy at 12 weeks, with nearly all patients (85%, 444/522 ) on moderate- or high-intensity statins, and the effect was durable through 52 weeks;
• significantly lowered high-sensitivity C-reactive protein (hsCRP), an important marker of the underlying inflammation associated with cardiovascular disease, by 19%, and the effect was durable through 52 weeks;

• showed no worsening of haemoglobin A1c (HbA_1c ) (- 0.21% vs. placebo) in patients with diabetes at 12 weeks;

• showed overall adverse event rates comparable with placebo (bempedoic acid 70% 366/522 vs. placebo 71% 182/257) at 52 weeks, and the proportion of patients with reported serious adverse events was similar compared with placebo (bempedoic acid 20% 106/522 vs. placebo 19% 48/257) at 52 weeks;
• showed adjudicated three-component major adverse cardiac event rates of 2.7% (14/522) with bempedoic acid and 4.7% (12/257) with placebo.

“The CLEAR Wisdom trial demonstrated that bempedoic acid provided additional LDL-C lowering in patients on background maximally-tolerated statin therapy and had an overall adverse event profile that was comparable to placebo,” said Anne C. Goldberg MD, FACP, FAHA, FNLA, Professor of Medicine, Division of Endocrinology, Metabolism and Lipid Research at Washington University, St. Louis and lead study author. “These results are consistent with the results reported from the largest long-term Phase 3 study of bempedoic acid, Study 1 or CLEAR Harmony, which were published earlier this year in the New England Journal of Medicine . Results across the Phase 3 development programme show that bempedoic acid has the potential to be a treatment option for high-risk patients who require additional LDL-C lowering.”

“We believe that bempedoic acid will address an important unmet need for patients who require additional LDL-C lowering and are not reaching their goals with existing oral lipid lowering therapies,” said Wolfgang Zierhut, MD, Head of Antithrombotic and Cardiovascular Medical Affairs Department at Daiichi Sankyo Europe. “Many patients remain at high risk of a cardiovascular event and need additional treatment options to achieve LDL-C goals. This is even more pertinent given that the latest guidelines suggest even lower LDL-C goals to provide optimal protection.”

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Design of Global Pivotal Phase 3 Study 2 (1002-047, also known as CLEAR Wisdom)
The 52-week, global, pivotal Phase 3 randomised, double-blind, placebo-controlled, multi-centre study evaluated the efficacy and safety of bempedoic acid 180 mg/day versus placebo. The study was conducted at 86 sites in North America and Europe. A total of 779 patients were randomised 2:1 to receive bempedoic acid or placebo. The primary efficacy objective was to assess the 12-week LDL-C lowering efficacy of bempedoic acid versus placebo. Secondary objectives included evaluating the safety and tolerability of bempedoic acid versus placebo, the 24-week and 52-week LDL-C lowering efficacy of bempedoic acid versus placebo, and bempedoic acid’s effects on other risk markers after 12 weeks of treatment, including hsCRP and HbA_1c , versus placebo.

Bempedoic Acid
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.^2,3 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.⁴ Due to its liver-specific mode of action, bempedoic acid has a reduced potential to induce the muscle-related side-effects commonly associated with statin therapy and provide additional LDL-C lowering on top of statin monotherapy in clinical trials.³

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.

About Daiichi Sankyo
Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 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 cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centred around rare diseases and immune disorders. For more information, please visit: www.daiichisankyo.com .

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¹ Goldberg AC, et al. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease. The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019;322(18):1780-1788. doi:10.1001/jama.2019.16585.
² Ray KK, et al . Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med . 2019;380:1022–32.
³ 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.
⁴ 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.

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