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– 14,032 Patients are Now Fully Enrolled in the CLEAR Cardiovascular Outcomes Trial –
– Expect CLEAR Cardiovascular Outcomes Trial to Conclude in the Second Half of 2022 –
ANN ARBOR, Mich., Sept. 05, 2019 (GLOBE NEWSWIRE) -- Esperion (NASDAQ:ESPR) today announced the completion of patient enrollment in the CLEAR Cardiovascular Outcomes Trial. The trial is designed to evaluate whether treatment with bempedoic acid reduces the risk of cardiovascular events in patients with statin intolerance (or “statin averse”) who have cardiovascular disease or are at high risk for cardiovascular disease. CLEAR Outcomes is an event-driven trial and will conclude once the predetermined number of major adverse cardiac events (MACE) endpoints occur. Based on estimated cardiovascular event rates, we expect to meet the target number of events in the second half of 2022.
“Completing enrollment in CLEAR Outcomes is an important milestone in the clinical development of bempedoic acid. Statin intolerant or averse patients, like those enrolled in CLEAR Outcomes, often face significant challenges in achieving their LDL-cholesterol targets," said Tim M. Mayleben, president and chief executive officer of Esperion. “We believe that all patients with elevated levels of LDL-cholesterol should have access to convenient, oral, once-daily, non-statin therapies that can reduce the risk of serious or even fatal cardiovascular events.”
“Phase 3 clinical trials demonstrated that bempedoic acid produces clinically important reductions in LDL-Cholesterol as well as hsCRP, a key marker of inflammation associated with cardiovascular disease,” said Stephen Nicholls, MBBS, PhD, FRACP, FACC, FESC, FAHA, FCSANZ, co-principal investigator of CLEAR Outcomes, and Director of MonashHeart, Monash Health and Professor of Cardiology, Monash University. “The CLEAR Cardiovascular Outcomes Trial builds on these results and will determine whether bempedoic acid can also reduce the risk of cardiovascular morbidity and mortality. Treatment of statin averse patients, like those enrolled in CLEAR Outcomes, represents a major unmet medical need that affects millions of patients.”
About the CLEAR Cardiovascular Outcomes Trial
CLEAR Outcomes is a Phase 3, event-driven, randomized, multicenter, double-blind, placebo-controlled trial designed to evaluate whether treatment with bempedoic acid reduces the risk of cardiovascular events. The primary endpoint of the study is the effect of bempedoic acid on major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization; also referred to as "four-component MACE"). CLEAR Outcomes is designed to provide 90 percent power to detect an approximately 15 percent relative risk reduction in the primary endpoint in the bempedoic acid treatment group as compared to the placebo group and is expected to complete with a minimum of 1,620 patients experiencing the primary endpoint.
Eligible patients at high risk (LDL-C >100 mg/dL in primary prevention) for cardiovascular disease or with cardiovascular disease (LDL-C between 100 mg/dL to 190 mg/dL in secondary prevention) and who are only able to tolerate less than the lowest approved daily starting dose of a statin and considered “statin averse”, were randomized to receive bempedoic acid 180 mg once-daily or placebo. The study enrolled 14,032 patients at over 1,200 sites in 32 countries.
Bempedoic acid and the bempedoic acid / ezetimibe combination tablet are in development to be cost-effective, convenient, once-daily, oral therapies for the treatment of patients with elevated low-density lipoprotein cholesterol (LDL-C) who need additional LDL-C lowering despite the use of currently accessible therapies. The U.S. Food and Drug Administration (FDA) has set a Prescription Drug User Fee Act (PDUFA) goal date for the completion of the bempedoic acid NDA review for February 21, 2020, and the PDUFA goal date for completion of the bempedoic acid / ezetimibe combination tablet NDA review for February 26, 2020.
For more information, go to clinicaltrials.gov: CLEAR Cardiovascular Outcomes Trial.
Bempedoic acid is our lead, non-statin, orally available, once-daily, LDL-C lowering therapeutic candidate, currently under review by the U.S. Food and Drug Administration (FDA). With a targeted mechanism of action, bempedoic acid is a first-in-class, ATP Citrate Lyase (ACL) inhibitor that reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor. Similar to statins, bempedoic acid also reduces hsCRP, a key marker of inflammation associated with cardiovascular disease. Completed Phase 3 studies conducted in more than 4,000 patients, with over 2,600 patients treated with bempedoic acid, demonstrated up to 18 percent placebo corrected LDL-C lowering when used with moderate- and high-intensity statins and 21 to 28 percent placebo corrected LDL-C lowering when used with low dose or no background statin.
Bempedoic Acid / Ezetimibe Combination Tablet
Through the complementary mechanisms of action of inhibition of cholesterol synthesis (bempedoic acid) and inhibition of cholesterol absorption (ezetimibe), the bempedoic acid / ezetimibe combination tablet is a non-statin, orally available, once-daily, LDL-C lowering therapeutic candidate, currently under review by the FDA. Inhibition of ATP Citrate Lyase (ACL) by bempedoic acid reduces cholesterol biosynthesis and lowers LDL-C by up-regulating the LDL receptor. Inhibition of Niemann-Pick C1-Like 1 (NPC1L1) by ezetimibe results in reduced absorption of cholesterol from the gastrointestinal tract, thereby reducing delivery of cholesterol to the liver, which in turn upregulates the LDL receptors. Phase 3 data demonstrated that this combination results in a 29 percent placebo corrected LDL-C lowering when used with maximally tolerated statins, a 44 percent LDL-C lowering when used with no background statin (post-hoc analysis), and a 34 percent reduction in high sensitivity C-reactive protein (hsCRP).
CLEAR Cardiovascular Outcomes Trial
The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined. Esperion initiated a global cardiovascular outcomes trial (CVOT) to assess the effects of bempedoic acid on the occurrence of major cardiovascular events in patients with, or at high risk for, cardiovascular disease (CVD) who are only able to tolerate less than the lowest approved daily starting dose of a statin and considered "statin averse." The CVOT — known as CLEAR Cardiovascular Outcomes Trial — is an event-driven, global, randomized, double-blind, placebo-controlled study that completed enrollment in August 2019 in 14,032 patients with hypercholesterolemia and high CVD risk at over 1,400 sites in 32 countries.
Esperion's Commitment to Patients with Hypercholesterolemia
High levels of LDL-C can lead to a build-up of fat and cholesterol in and on artery walls (known as atherosclerosis), potentially leading to cardiovascular events, including heart attack or stroke. In the U.S., 96 million people, or more than 37 percent of the adult population, have elevated LDL-C. There are approximately 18 million people in the U.S. with atherosclerotic cardiovascular disease (ASCVD) who live with elevated levels of LDL-C despite taking maximally tolerated lipid-modifying therapy — including individuals considered statin averse — leaving them at high risk for cardiovascular events1. More than 50 percent of ASCVD patients who are not able to reach their LDL-C goals with statins alone need less than a 40 percent reduction to reach their LDL-C threshold2.
Esperion's mission as the Lipid Management Company is to deliver once-daily, oral therapies that complement existing oral drugs to provide the additional LDL-C lowering that these patients need.
The Lipid Management Company
Esperion is the Lipid Management Company passionately committed to developing and commercializing convenient, cost-effective, complementary, once-daily, oral therapies for the treatment of patients with elevated LDL-C. Through scientific and clinical excellence, and a deep understanding of cholesterol biology, the experienced Lipid Management Team at Esperion is committed to developing new LDL-C lowering therapies that will make a substantial impact on reducing global cardiovascular disease, the leading cause of death around the world. Bempedoic acid and the bempedoic acid / ezetimibe combination tablet are targeted therapies that are being developed to significantly lower elevated LDL-C levels in patients with hypercholesterolemia, including patients inadequately treated with current lipid-modifying therapies. For more information, please visit www.esperion.com and follow us on Twitter at https://twitter.com/EsperionInc.
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding the regulatory approval pathway for bempedoic acid and the bempedoic acid / ezetimibe combination tablet and the therapeutic potential of, clinical development plan for, bempedoic acid and the bempedoic acid / ezetimibe combination tablet, including Esperion's timing, designs, plans and announcement of results regarding its CLEAR Cardiovascular Outcomes Trial and other ongoing clinical studies for bempedoic acid and the bempedoic acid / ezetimibe combination tablet, timing for the review and approval of the NDAs and the MAAs and Esperion's expectations for the market for therapies to lower LDL-C, including the market adoption of bempedoic acid and the bempedoic acid / ezetimibe combination tablet, if approved. Any express or implied statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause Esperion's actual results to differ significantly from those projected, including, without limitation, delays or failures in Esperion’s studies, that positive results from a clinical study of bempedoic acid may not be sufficient for FDA or EMA approval or necessarily be predictive of the results of future or ongoing clinical studies, that notwithstanding the completion of Esperion’s Phase 3 clinical development program for LDL-C lowering, the FDA or EMA may require additional development in connection with seeking regulatory approval, that existing cash resources may be used more quickly than anticipated, and the risks detailed in Esperion's filings with the Securities and Exchange Commission. Esperion disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.
1 Esperion market research on file: research project interviewing 350 physicians. Esperion Therapeutics, Inc. Sept-Oct 2018.
2 Data on file: analysis of NHANES database. Esperion Therapeutics, Inc. 2018.