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- Biodedic acid is an oral inhibitor of ATP citrate lyase (ACL) that reduces the synthesis of cholesterol and fatty acids in the liver.
- Study 1 is the largest of the five phases of the third phase of the comprehensive program of studies on the benefits of bempedic acid in patients requiring further lowering of low-density lipoprotein cholesterol (LDL-C)
- In the past 52 weeks, bempedic acid has been shown to be well tolerated and not badociated with higher overall adverse effects than those treated with placebo.
- Treated patients had lower rates of onset or worsening of diabetes compared with those on placebo[1]
- Search by teacher Kausik Ray published in the March 14, 2019 The New England Journal of Medicine (NEJM)
Munich, Germany and ANN ARBOR, Michigan, March 14, 2019 / PRNewswire / – Daiichi Sankyo Europe GMbH (hereinafter referred to as "Daiichi Sankyo") and Esperion Therapeutics (NASDAQ: ESPR) announced today the release of the results of the safety study on the subject. Bempedic acid conducted on 2,230 patients, phase 3, long-term NEJM. The document can be found online here.
Bempedoic acid is being developed as a once-a-day oral therapy for the treatment of patients with elevated LDL-C levels. Bempedic acid and the bempedic acid / ezetimibe combination are currently undergoing regulatory review for marketing authorization by the European Medicines Agency (EMA). A decision is expected in the first half of 2020.
Study 1, also known as CLEAR Harmony (reduction of cholesterol via bapedoic acid, an ACL inhibitor regimen), is the largest study of the CLEAR Phase 5 research program. designed to provide significant evidence of the benefits of bempedoic acid in patients in need. additional lowering of LDL-C. The first study evaluated the safety, tolerability, and long-term efficacy of 180 mg bortezopic acid versus placebo in 2,230 patients at high risk for atherosclerotic cardiovascular disease (ASCVD). ) and insufficiently controlled by current lipid-lowering treatments, including maximally tolerated statins.
the NEJM The publication highlights the results of the primary endpoint for evaluating adverse event rates over a 52-week period, as well as key evaluation criteria for effectiveness at 12 weeks, including bempedoic acid:[1]
- significant decrease in LDL-C by 18.1% (p <0.001) with maximally tolerable statin therapy
- 22% significant reduction in hsCRP, an important marker of underlying inflammation badociated with cardiovascular disease
- treated patients had lower rates of diabetes or worsening diabetes compared to placebo patients (3.3% vs. 5.4%)
- did not result in an increase in overall adverse events compared to placebo (78.5% vs. 78.7%) and the proportion of patients in whom serious adverse events were reported was small and similar to placebo (14.5% vs. 14.0%).
- did not result in increased rates of discontinuation due to significant adverse events of muscle, myalgia and muscle weakness compared with placebo (2.1 % against 1.9%)
- showed fewer major cardiac adverse events evaluated compared to placebo (4.6% vs. 5.7%)
- has been observed to be well tolerated.
"The release of the largest study on Bempedoic acid to date still confirms what great experts have stated, namely that bempedic acid is a well-tolerated and effective potential treatment that can reduce LDL-C and the hsCRP, the results of this study support Daiichi Sankyo's long-term commitment to cardiovascular care in Europe. " Wolfgang Zierhut, MD, Executive Director of Medical Affairs and Head of Thrombosis and Cardiovascular Disease at Daiichi Sankyo Europe.
"The latest study shows that bempedic acid could be another addition to the arsenal of oral cholesterol-lowering treatments given once a day to patients.At the end, these latest studies show that treatment is not only generally well tolerated, but that it is comparable to placebo, but that, added to high-intensity statin therapy, it can help further reduce LDL-C levels, "said the professor. Kausik Ray, School of Public Health at Imperial College London, who led the study. "Although this is not a results study, the same article in the same issue of the journal comparing the mechanism of lowering cholesterol with bempedic acid with statins using genetics suggests that we can hope we expect a similar benefit to statins per mmol / L LDL lowering The current trial, 'CLEAR OUTCOMES', specifically tests the long-term safety and seeks to determine whether this approach reduces the risk of cardiovascular disease in addition to lowering cholesterol. "
Design of the first phase 3 pivotal study worldwide
The randomized, randomized, double-blind, placebo-controlled, phase 3, phase 3, multi-center study evaluated the long-term safety and tolerability of 180 mg / day bortezopic acid versus placebo in high-risk patients with ASCVD and / or heterozygous patients. Familial hypercholesterolemia (HeFH) with LDL-C levels of at least 70 mg / dL (1.8 mmol / L) insufficiently controlled by standard lipid-lowering therapies, including maximally tolerated statin therapy. The study was conducted on 117 sites in the United States. Canada and Europe . A total of 2,230 patients were randomized 2: 1 to receive bortezic acid or placebo. The secondary objective was to evaluate the efficacy of bempedoic acid against LDL cholesterol for 12 weeks compared with placebo. Tertiary objectives were to evaluate the effect of bempedic acid on other lipid parameters and on risk markers, including hsCRP.
An open extension study (1002-050) was launched in early 2017 and was fully recruited with 1,462 patients.
Fixed dose combined tablet of bempedic acid and ezetimibe
Due to the complementary mechanisms of action of inhibiting the synthesis of cholesterol (bempedoic acid) and inhibition of cholesterol absorption (ezetimibe), the tablet badociated with a fixed dose Biodedic acid / ezetimibe is a non-statin, available orally, administered once daily, lowering LDL-C at least once a day therapy. Inhibition of ATP Citrate Lyase (ACL) by bempedoic acid reduces cholesterol biosynthesis and decreases LDL-C by positively regulating the LDL receptor. Inhibition of ezetimibe on Niemann-Pick C1-Like 1 (NPC1L1) results in a reduction in the absorption of cholesterol by the gastrointestinal tract, which reduces cholesterol intake to the liver, which in turn upregulates LDL receptors. Phase 3 data showed that this well tolerated combination resulted in a 35% reduction in LDL-C when used with maximally tolerated statins, a 43% reduction in LDL-C alone and a 34% reduction in the high sensitivity of C-LD. reactive protein (hsCRP). The rates of adverse events occurring during treatment, muscle-related adverse events and discontinuations were similar in the groups treated with bempedoic acid and placebo.[2]
Bipedoic acid
Due to its targeted mechanism of action, bempedoic acid is a single oral single dose ATP citrate lyase (ACL) inhibitor administered once daily. It reduces the biosynthesis of cholesterol and fatty acids, as well as LDL-C by positively regulating LDL receptors. . Just like statins, bempedoic acid also reduces highly sensitive C-reactive protein (hs-CRP), a key marker of inflammation badociated with cardiovascular disease.[3] Biodedic acid is a prodrug that requires activation with very long-chain acyl-CoA synthase-1 (ACSVL1). In addition, it has been shown that the absence of skeletal muscle ACSVL1 provides a mechanistic basis for bempedoic acid to potentially avoid the myotoxicity badociated with statin therapy.[4] Phase 2 and 3 studies in nearly 4,800 patients and approximately 3,100 patients treated with bempedic acid resulted in a further 20% reduction in LDL-C when they were used with maximally tolerated statins, up to 30% reduction of LDL-C monotherapy, 35% reduction of LDL-C in combination with ezetimibe when it is used with maximally tolerated statins and reduction of up to 48% of LDL-C in combination with ezetimibe monotherapy.[5] The rates of adverse events occurring during treatment, muscle-related adverse events and discontinuations were similar in the groups treated with bempedoic acid and placebo.[3]
The effect of bempedoic acid on cardiovascular morbidity and mortality has not yet been determined. The company has launched a global trial on cardiovascular outcomes to evaluate the effects of bempedic acid on the occurrence of major cardiovascular events in patients with cardiovascular disease or with a history of cardiovascular disease. high risk of cardiovascular disease, which can only tolerate less than the minimum dose exposure. approved daily starting dose of a statin and considered "statin intolerant". CVOT – known as CLEAR Outcomes – is a randomized, double-blind, placebo-controlled, placebo-controlled, placebo-controlled study that is expected to include approximately 12,600 patients with hypercholesterolemia and high risk CVD in approximately 30 countries.[6]
About Daiichi Sankyo
The Daiichi Sankyo Group is dedicated to creating and delivering innovative pharmaceutical products that address the diverse and unmet medical needs of patients in both mature and emerging markets. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees worldwide have a rich heritage of innovation and a strong portfolio of promising new drugs. to help the people. In addition to a strong portfolio of drugs for hypertension and thrombotic disorders, the Daiichi Sankyo Group is focused on becoming a "global pharmaceutical innovator with competitive advantages in oncology", as well as innovative new treatments in oncology, including: 39, immuno-oncology, with emphasis on new areas such as pain management, neurodegenerative diseases, heart and kidney diseases and other rare diseases. For more information, please visit: www.daiichisankyo.com.
Escrow commitment to patients with hypercholesterolemia
High levels of LDL-C can lead to fat and cholesterol build-up in and on artery walls (called atherosclerosis), potentially leading to cardiovascular events, including a heart attack or stroke. In the United States, 96 million people, or more than 37% of the adult population, have high LDL-C levels. In the United States, approximately 18 million people with atherosclerotic cardiovascular disease (ASCVD) live with high levels of LDL-C despite the treatment maximally tolerant of lipid-modifying lipids, including individuals considered to be statin intolerant, exposing to a high risk of cardiovascular events. More than 50% of ASCVD patients who can not achieve their LDL-C goals with statins alone require a reduction of less than 40% to reach their LDL-C level.
As a lipid management company, Esperion's mission is to provide once-a-day oral therapies, in addition to existing oral medications, to further reduce the LDL-C levels that these patients need.
The lipid management company
Esperion is the lipid management company that is pbadionate about developing and commercializing complementary, cost-effective, convenient, once-a-day oral therapies for the treatment of patients with high LDL-C. Through scientific and clinical excellence and in-depth knowledge of cholesterol biology, Esperion's experienced lipid management team is committed to developing new treatments that reduce LDL-C that will have a substantial impact on reducing cholesterol levels. cardiovascular diseases worldwide; the leading cause of death in the world. Biodedic acid and the Company's lead product candidate, the combination bempedic acid and ezetimibe tablets, are targeted therapies that have demonstrated a significant reduction in elevated LDL-C levels in patients with hypercholesterolemia. including in patients inadequately treated with current lipid modification treatments. For more information, visit www.esperion.com and follow us on Twitter at the address 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 a statement regarding the regulatory approval process for the bempedohydroic acid / ezetimibe tablet and bempedic acid, as well as the therapeutic potential of this clinical development plan. with regard to the combination of bempedoic acid / ezetimibe and bempedoic acid, including timing, designs, plans and announcement of results regarding its CLEAR Outcomes study and other ongoing clinical studies on Bempedic acid and the combination of bempedoic acid / ezetimibe, Esperion market expectations of treatments to reduce LDL cholesterol, including the market adoption of bempedic acid and the combination of bempedic acid / ezetimibe, as applicable, the expected milestones described in this press release and Esperion's cash position and financial outlook. Any express or implied statement contained in this press release that is not a statement of historical fact may be considered a forward-looking statement. Forward-looking statements involve risks and uncertainties that could cause Esperion's actual results to differ materially from those projected, including, without limitation, delays or failures in Esperion's studies that Positive results from a clinical study on bempedoic acid may not be sufficient for the FDA or the approval of EMA or necessarily be predictive of the results of future or ongoing clinical studies. Regardless of the completion of Esperion's Phase 3 clinical development program for LDL-C reduction, the FDA or EMA may require further development as part of the ongoing application. regulatory approval, this EHR is able to successfully commercialize the bempedoic acid / ezetimibe tablet and bempedic acid, if approved, that existing cash resources can be used faster than anticipated and that the risks described in Esperion's filings with the Securities and Exchange Commission. Esperion disclaims any obligation or obligation to update or revise the forward-looking statements contained in this press release, except to the extent required by law.
Product communication contact:
Lydia Worms
Daiichi Sankyo Europe GmbH
+49 (89) -7808751
[email protected]
Investor contact:
Alex Schwartz
Esperion
734-249-3386
[email protected]
[1] Ray K, et al. Safety and efficacy of bempedoic acid. N Engl J Med 2019; 380: 1022-1032. DOI: 10.1056 / NEJMoa1803917
[2] Preliminary results of the Phase 3 study on the combined bempedic acid and ezetimibe combination pill. Esperion Investor Presentation. August 27, 2018. Available at https://investor.esperion.com/static-files/1639de53-9494-4299-98a5-0b6f1317678a. Last access March 8, 2019.
[3] Preliminary results of phase 3 of study 2 and cumulative results of the phase 3 program. Esperion Investor Presentation. October 29, 2018. Available at https://investor.esperion.com/static-files/32936da0-96f9-40e5-a12b-bd00ece6698d. Last access March 8, 2019.
[4] Pinkosky L et al. Inhibition of ATP-specific citrate lyase of the liver 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 statin intolerance and at high risk of acquiring cardiovascular disease with bempedic acid (ETC-1002) or placebo (CLEAR results). Available at https://clinicaltrials.gov/ct2/show/NCT02993406?term=bempedoic+acid&rank=4. Last access December 12, 2018.
March 2019 Labor Code: BEM / 19/0002
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