MUNICH and ANN ARBOR, Michigan, April 2, 2019
MUNICH and ANN ARBOR, Michigan, April 2, 2019 PRNewswire/ -- Daiichi Sankyo Europe GMbH (hereafter, 'Daiichi Sankyo') and Esperion Therapeutics (NASDAQ: ESPR) announced today that results from the 345 patient, 24-week, Phase 3 double-blind, placebo-controlled study of bempedoic acid (CLEAR Serenity, also known as Study 3) were published in the Journal of the American Heart Association (JAHA). Bempedoic acid is being developed as a complementary, convenient, once-daily, oral therapy for the treatment of patients with elevated low-density lipoprotein cholesterol (LDL-C). Bempedoic acid and the bempedoic acid / ezetimibe combination tablet new drug applications are under regulatory review for marketing authorisation by the European Medicines Agency (EMA) and have been submitted to the United States Food and Drug Administration (FDA).
The JAHA publication highlights that bempedoic acid met the primary efficacy endpoint and significantly lowered LDL-C by 21% (absolute reduction -36mg/dL) at 12-weeks.1
The publication also shows key secondary efficacy endpoints at 12 and 24 weeks and safety and tolerability outcomes, demonstrating that bempedoic acid:1
"In the challenging group of patients with statin intolerance, CLEAR Serenity demonstrates that bempedoic acid reduced LDL-C significantly more than placebo. Patients taking bempedoic acid reported less frequent occurrences of myalgia and muscular weakness compared with placebo. These results demonstrate bempedoic acid could offer a well-tolerated and effective oral therapeutic option especially for the millions of patients needing LDL-C lowering but have difficulty tolerating statin treatment due to muscle-related side effects," said Ulrich Laufs, MD, PhD.
"For patients who have experienced the side effects commonly attributed to statin treatment and can't or won't take statins, there is an urgent need to significantly lower their LDL-C and hsCRP levels. The publication of the CLEAR Serenity Study in the Journal of American Heart Association further demonstrates that bempedoic acid could be a well-tolerated and efficacious treatment option for hypercholesterolemia patients, including those patients considered statin intolerant," said Wolfgang Zierhut, MD, Head of Antithrombotic and Cardiovascular Medical Affairs Department at Daiichi Sankyo Europe.
Design of Global Phase 3 Study 3 (1002-046, also known CLEAR Serenity)
The 24-week, global pivotal Phase 3 randomised, double-blind, placebo-controlled, multicenter study evaluated the LDL-C lowering efficacy and safety of bempedoic acid 180 mg/day versus placebo added to background lipid-modifying therapy in patients with hypercholesterolemia who are considered statin intolerant. The study was conducted at 67 sites in the U.S. and Canada. A total of 345 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 24-week LDL-C lowering efficacy of bempedoic acid versus placebo and its effects on other risk markers after 12 weeks of treatment, including hsCRP. Safety and tolerability were evaluated through continuous monitoring of patients.
Bempedoic Acid / Ezetimibe Fixed Dose 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 fixed dose combination tablet is a non-statin, orally available, once-daily, LDL-C lowering therapy. 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 well tolerated combination results in a 35% lowering of LDL-C when used with maximally tolerated statins, a 43% lowering of LDL-C when used as a monotherapy, and a 34% reduction in high sensitivity C-reactive protein (hsCRP). Rates of treatment-emergent adverse events, muscle-related adverse events and discontinuations were similar in the bempedoic acid and placebo treatment groups.2
With a targeted mechanism of action, bempedoic acid is a first-in-class, complementary, oral, once-daily ATP Citrate Lyase (ACL) inhibitor that reduces cholesterol and fatty acid biosynthesis and lowers LDL-C by up-regulating the LDL receptor. Similar to statins, bempedoic acid also reduces high sensitivity C-reactive protein (hs-CRP), a key marker of inflammation associated with cardiovascular disease.3 Bempedoic acid is a prodrug that requires activation by the very long-chain acyl-CoA synthetase-1 (ACSVL1). Furthermore, it was demonstrated that the absence of ACSVL1 in skeletal muscle provides a mechanistic basis for bempedoic acid to potentially avoid the myotoxicity associated with statin therapy.4 Completed Phase 2 and Phase 3 studies conducted in almost 4,800 patients, and approximately 3,100 patients treated with bempedoic acid, have produced an additional 20% LDL-C lowering when used with maximally tolerated statins, up to 30% LDL-C lowering as monotherapy, 35% LDL-C lowering in combination with ezetimibe when used with maximally tolerated statins and up to 48% LDL-C lowering in combination with ezetimibe as monotherapy.5 Rates of treatment-emergent adverse events, muscle-related adverse events and discontinuations were similar in the bempedoic acid and placebo treatment groups.3
The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined. The company 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 intolerant." The CVOT — known as CLEAR Outcomes — is an event-driven, randomised, double-blind, placebo-controlled study expected to enroll approximately 12,600 patients with hypercholesterolemia and high CVD risk at over 1,000 sites in approximately 30 countries.6
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.
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% 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 intolerant — leaving them at high risk for cardiovascular events. More than 50% of ASCVD patients who are not able to reach their LDL-C goals with statins alone, need less than a 40% reduction to reach their LDL-C threshold.
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 commercialising complementary, cost-effective, convenient, 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 company's lead product candidate, the bempedoic acid / ezetimibe combination tablet, are targeted therapies that have been shown 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.
Forward Looking Statement: Esperion
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 the bempedoic acid / ezetimibe combination tablet and bempedoic acid and the therapeutic potential of, clinical development plan for, the bempedoic acid / ezetimibe combination tablet and bempedoic acid, including Esperion's timing, designs, plans and announcement of results regarding its CLEAR Outcomes study and other ongoing clinical studies for bempedoic acid and the bempedoic acid / ezetimibe combination tablet, 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, the expected upcoming milestones described in this press release, and Esperion's cash position and financial outlook. 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 programme for LDL-C lowering, the FDA or EMA may require additional development in connection with seeking regulatory approval, that DSE is able to successfully commercialise the bempedoic acid / ezetimibe combination tablet and bempedoic acid, if approved, 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 Laufs U, et al. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. JAHA 2019.
2 Top-Line Results from the Bempedoic Acid / Ezetimibe Combination Pill Phase 3 Study. Esperion Investor. JAHA 2019 Presentation. Aug 27, 2018. Available at https://investor.esperion.com/static-files/1639de53-9494-4299-98a5-0b6f1317678a. Last accessed March 8, 2019.
3 Phase 3 Top-Line Results from Study 2 & Cumulative Phase 3 Program Results. Esperion Investor Presentation. Oct 29, 2018. Available at https://investor.esperion.com/static-files/32936da0-96f9-40e5-a12b-bd00ece6698d. Last accessed March 8, 2019.
4 Pinkosky L et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nature. 2016: 10.1038.
5 Thompson PD, et al. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol (2016) 10, 556–567.
6 Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated with Bempedoic Acid (ETC-1002) or Placebo (CLEAR Outcomes). Available at https://clinicaltrials.gov/ct2/show/NCT02993406?term=bempedoic+acid&rank=4. Last accessed December 12, 2018.
Lydia Worms (Europe)
Daiichi Sankyo Europe GmbH
Communications & Product PR Europe
+49 (89) 7808751
April 2019 BEM/19/0001