Bempedoic Acid Significantly Reduces LDL-Cholesterol on Top of Statin Therapy: Results of the CLEAR Wisdom Trial, Published in the Journal of the American Medical Association

• Bempedoic acid is an oral, once-daily ATP citrate lyase (ACL) inhibitor that reduces cholesterol synthesis in the liver and is currently undergoing regulatory review
• Bempedoic acid lowered LDL-Cholesterol by 17% on top of maximally-tolerated statin therapy at 12 weeks, and the effect was durable through 52 weeks¹
• Overall adverse events in the bempedoic acid treatment arm were comparable to placebo over 52 weeks¹

MUNICH, Germany, (November 12, 2019) – 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.[i]

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.”

- ENDS -

[i] 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