Delving into the Latest Updates on Bempedoic acid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Bempedoic acid (USAN/INN), Nilemdo, ESP-55016

+ [2]

Target

ACL

Mechanism

ACL inhibitors(ATP-citrate synthase inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseOther Diseases

Active Indication

Cardiovascular DiseasesMyocardial InfarctionPrimary Hyperlipidemia+ [7]

Inactive Indication

Diabetes Mellitus, Type 2Hypertension

Originator Organization

Esperion Therapeutics, Inc.

Active Organization

Daiichi Sankyo Europe GmbH

Esperion Therapeutics, Inc.Daiichi Sankyo (Schweiz) AG

+ [1]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (21 Feb 2020),

AtherosclerosisHeterozygous familial hypercholesterolemia

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC19H36O5

InChIKeyHYHMLYSLQUKXKP-UHFFFAOYSA-N

CAS Registry738606-46-7

Statin intolerance occurs in up to 15-20% of treated patients. The combined use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors with ezetimibe is commonly performed in these patients, and has been associated with an estimated LDL-C reduction of 65-70%. This drug combination may be insufficient to reach the LDL-C target in high- and very-high-risk patients with statin intolerance, also considering the goals recommended by the current international guidelines. Also, PCSK9 inhibitor dosage escalations frequently fail to achieve the target. Doubling the dosage of alirocumab from 75 mg to 150 mg, when administrated as monotherapy, determines a further reduction of only 3,6% of LDL-C serum level. The full dose of Evolocumab (420 mg every two weeks), was approved only in the setting of homozygous familiar hypercholesterolemia.
Bempedoic acid is an oral, once-daily prodrug, metabolized in the liver to an active inhibitor of ATP-citrate lyase, blocking cholesterol synthesis upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and thereby increasing hepatic expression of the LDL receptor and decreasing circulating LDL-C levels.
The CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen) Harmony trial demonstrated that bempedoic acid in addition to maximally tolerated statin therapy did not lead to a higher incidence of adverse events compared to placebo and significantly lowered LDL-C levels. In the CLEAR Serenity study, bempedoic acid showed a safe and effective profile compared with placebo in patients with statin intolerance. In the CLEAR Tranquility, it provided an oral therapeutic option complementary to ezetimibe in patients intolerant to high-dose statins who required additional LDL-C lowering.
The synergistic effect of bempedoic acid plus PCSK9 inhibitors has been investigated by one phase 2 trial (NCT03193047), which showed a statistical superiority of bempedoic acid plus evolocumab strategy versus placebo plus evolocumab in terms of percent change in LDL-C up to 2 months. To date, no randomized phase 3 clinical trial have evaluated the effect of bempedoic acid in association with anti-PCSK9 and ezetimibe in statin-intolerant patients not attaining the recommended LDL-C target.
The investigators hypothesized that the association of bempedoic acid with PCSK9 inhibitors and ezetimibe may be safe and effective in reducing LDL-C in statin-intolerant patients.

Start Date01 May 2024

Sponsor / Collaborator

University of Salerno

NCT06035874 / RecruitingNot ApplicableIIT

Effect of Bempedoic Acid on Liver Fat in Individuals With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes: Randomized Controlled Trial

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome and dyslipidemia.
Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH. Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the current study is planned to evaluate the effect of bempedoic acid versus standard treatment on liver and pancreatic fat content in patients with NAFLD

Start Date15 Oct 2023

Sponsor / Collaborator-

100 Clinical Results associated with Bempedoic acid

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100 Translational Medicine associated with Bempedoic acid

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100 Patents (Medical) associated with Bempedoic acid

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310

Literatures (Medical) associated with Bempedoic acid

09 Feb 2024·European heart journal. Acute cardiovascular care

Quality control to improve LDL-cholesterol management in patients with acute coronary syndromes based on the ACS EuroPath IV project

Article

Author: Catapano, Alberico L ; Jukema, J Wouter ; Schiele, François ; Zaman, Azfar ; Laufs, Ulrich ; De Caterina, Raffaele ; Sionis, Alessandro

Abstract:

Aims:

We performed quality control of lipid-lowering therapy (LLT) in patients with acute coronary syndrome (ACS), with a view to proposing corrective actions.

Methods and results:

Using a Define Measure Analysis Improve Control (DMAIC) approach applied to data from the ACS EuroPath IV survey, we measured attainment of two quality indicators (QIs) related to lipid-lowering treatment: (i) prescription of high-intensity statins (or equipotent treatment) before discharge, and (ii) proportion with LDL-cholesterol <55 mg/dL (1.4 mmol/L) during follow-up. A total of 530 European cardiologists responded and provided data for up to 5 patients from their centre, for acute and follow-up phases. Corrective measures are proposed to increase the rate of attainment of both QIs. Attainment of the first QI was measured in 929 acute-phase patients, 99% had LLT prescribed at discharge and 75% of patients fulfilled the first QI. Attainment of the second QI was assessed in 1721 patients with follow-up. The second QI was reached in 31% of patients. The DMAIC approach yielded 10 potential changes in prescription, 3 for the first and 7 for the second QI. The overall strategy is ‘Fire to Target’, i.e. early intensification of the LLT using statins, ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type-9 inhibitors, and is presented as an algorithm for routine application.

Conclusion:

Quality control for LLT, based on the ACS EuroPath IV survey, detected 10 potential changes in prescription that could enhance attainment of 2 QIs. Whether the Fire to Target strategy will be adopted and effective needs to be assessed in further steps of the EuroPath Quality programme.

01 Feb 2024·Current opinion in lipidology

Bempedoic acid: new evidence and recommendations on use

Review

Author: Pećin, Ivan ; Reiner, Željko ; Banach, Maciej ; Paponja, Kristina

Purposes of review:

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. Recognizing the importance of dyslipidemia treatment in the prevention of cardiovascular events has become a part of standard clinical practice. Desired values of LDL cholesterol (LDL-C) have become lower and lower in the last few decades, as evidenced by the most recent guidelines. Therefore, efforts to lower LDL cholesterol concentrations with conventional therapies and combinations of lipid-lowering therapy may not be successful in a high proportion of patients.

Recent findings:

Bempedoic acid is a novel agent, first in-class ATP Citrate Lyase (ACL) inhibitor, which targets biosynthesis of the cholesterol in the liver. Considering the results of phase 3 studies, it has been approved for sole use for dyslipidemia treatment for patients who are statin-intolerant or in combination with statin-ezetimibe for those suffering from familial hypercholesterolemia or ASCVD and unable to reach targeted LDL-C values.

Summary:

Bempedoic acid has proven beneficial for further reduction of LDL cholesterol for targeted groups of patients. It is not only efficient but also a well tolerated, affordable, and available agent whose place in lipid-lowering management is yet to be fully understood with new data collected from ongoing clinical research. In this review we suggest the place of bempedoic acid in lipid-lowering management.

01 Feb 2024·Current problems in cardiology

Efficacy and outcomes of Bempedoic acid versus placebo in patients with statin-intolerance: A pilot systematic review and meta-analysis of randomized controlled trials

Review

Author: Mahalwar, Gauranga ; Changez, Mah I Kan ; Shamim, Urooj ; Tariq, Muhammad Daoud ; Sohail, Amir Humza ; Goyal, Aman ; Mushtaq, Fiza

INTRODUCTION:

Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other hyperlipidemic drugs such as statins. However, its efficacy in patients with statin intolerance is controversial with inconsistent results among studies.

MATERIALS AND METHODS:

An electronic literature search was performed using various databases such as Medline, Google Scholar, and the International Registry of Clinical Trials. The primary endpoint was the change in LDL-C levels. The secondary endpoints included changes in HDL-C, non-HDL-C, triglycerides (TG), clinical outcomes such as MACE, all-cause mortality (ACM), cardiovascular mortality, myocardial infarction (MI), and additional safety outcomes. The least-square mean (LSM) percent change for assessing changes in lipid parameter levels from the baseline and the risk ratio (RR) were used for the evaluation of binary endpoints, with statistical significance set at p<0.05. Random-effects meta-analyses were performed for all the outcomes.

RESULTS:

Our analysis included 5 randomized controlled trials (RCTs) with a total of 18,848 participants. BA showed a significant reduction in LDL-C [LSM difference in %: -25.24; 95 % CI: -30.79 to -19.69; p < 0.00001], total cholesterol [LSM difference in %:-21.28; 95 % CI:-30.58 to-11.98; p < 0.00001], non-HDL-C [LSM difference in %: -23.27; 95 % Cl: -29.80 to -16.73 p < 0.00001], and HDL-C [LSM difference in %:-3.37, 95 % CI:-3.73 to-3.01, p < 0.00001] compared to placebo. In terms of clinical efficacy, BA was associated with a lower risk of coronary revascularization [RR:0.81; 95 % CI:0.66 to 0.99; p = 0.04], hospitalization for unstable angina [RR:0.67; 95 % CI:0.50 to 0.88; p = 0.005], and myocardial infarction [RR:0.76; 95 % CI:0.66 to 0.88;p = 0.0004]. No significant difference was observed in MACE [RR:0.81; p = 0.15], ACM [RR:0.86; p = 0.46], cardiovascular-related mortality [RR:0.79; p = 0.44], and stroke [RR:0.83; p = 0.08] between the two groups. In terms of safety efficacy, the risk for myalgia was significantly lower in BA-treated patients than in placebo [RR:0.80; p = 0.0002], while the risk for gout [RR:1.46; p < 0.0001] and hyperuricemia [RR:1.93; p < 0.00001] was higher for BA than for placebo. The risks for other adverse effects, such as neurocognitive disorder, nasopharyngitis urinary tract infection, upper respiratory infection, muscular disorder, and worsening hyperglycemia/DM were comparable between the two groups.

CONCLUSION:

Our analysis demonstrated that BA significantly reduced the levels of LDL-C, total cholesterol, non-HDL-C, HDL-C, ApoB, and hs-CRP compared with the placebo group. Additionally, patients who received BA had a lower likelihood of coronary revascularization and hospitalization due to unstable angina, MI, and myalgia. Further large-scale RCTs are required to generate more robust evidence.

44

News (Medical) associated with Bempedoic acid

28 Jun 2024

·www.biopharmadive.com

PTC faces another Duchenne drug rejection; Coherus sells Humira biosimilar

Today, a brief rundown of news from PTC Therapeutics, Esperion Therapeutics and Coherus Biosciences, as well as updates from Sanofi, Lantheus Holdings and Forbion that you may have missed.Drug regulators in Europe have, for a third time, recommended against renewing the approval of PTC TherapeuticsDuchenne muscular dystrophy medicine Translarna. The European Medicines Agency panel had been asked to re-evaluate PTCs application after the European Commission, in an unusual step, rejected its recommendation and suggested it consider data from patient registries and real-world use. That evidence still doesnt prove Translarna is effective, the panel said Friday. PTC will again seek another opinion, during which time Translarna will remain on the market in Europe. Ben FidlerEsperion Therapeutics said Friday it has sold rights to sales royalties in Europe for its cholesterol-lowering pill bempedoic acid to Omers Life Sciences for $305 million.Omers will own those royalties until its received 1.7-times its initial investment, after which Esperion will reclaim rights. Esperion will use some of the proceeds to pay off a loan from Oberland Capital, and is still eligible to receive up to $300 million in sales-based milestone payments under a licensing deal with Daiichi Sankyo. Jonathan GardnerCoherus BioSciences is selling rights to Yusimry, a biosimilar version of Humira, to Hong Kong King-Friend Industrial for $40 million in cash. The biosimilaris the second Coherus has divested this year as part of a plan to focus its business on branded cancer drugs. It won U.S. approval for its first, a cancer immunotherapy called Loqtorzi, in 2023. Jonathan GardnerSanofi is investing $40 million in Vigil Neuroscience, a biotech developing drugs for neurodegenerative diseases. The deal gives Sanofi an exclusive right of first negotiation to license from Vigil an experimental antibody aimed at the protein TREM2. Vigil has one such medicine in early-stage testing for Alzheimers disease treatment. The biotech, which went public in 2022but has lost much of its value since, said the deal will extend its cash runway into 2026. Gwendolyn WuLantheus Holdings, a developer of radiopharmaceutical drugs and diagnostics, paid $35 million to acquire rights to what it calls a radiotheranostic pair from Life Molecular Imaging. The pair consists of a lutetium-based treatment and a gallium-based diagnostic for prostate cancer, both aimed at the gastrin-releasing peptide receptor. Discovered at the Universities Bern and Basel, the pair was initially developed by Bayer and then licensed to Life Molecular. Lantheus plans to start a Phase 1/2a study of the radiopharmaceutical next year, with the gallium-based agent used as a companion diagnostic. Ned PagliaruloEuropean venture capital firm Forbion has hired former Dyne Therapeutics CEO Josh Brumm to help expand its presence in the U.S. Brumm will serve as a general partner and support Forbions current portfolio companies as well as source new opportunities in the U.S. and Europe, the firm said Thursday. Though Forbion is based in the Netherlands, about 30% of its investments are in the U.S. and Canada. Gwendolyn Wu '

License out/inDrug Approval

26 Jun 2024

·www.fiercebiotech.com

Arrowhead axes heart disease drug, goes all in on another as pipeline progress drives costs up

Arrowhead Pharmaceuticals hopes to find a partner for the now-deprioritized zodasiran. With two cardiovascular disease candidates in or near phase 3, RNAi specialist Arrowhead Pharmaceuticals has dropped one prospect and thrown its weight behind the other to manage its spending. Arrowhead’s cardiometabolic disease pipeline is led by plozasiran and zodasiran, RNAi molecules that hit different targets: APOC3 and ANGPTL3, respectively, but have similar uses. Both molecules are designed to boost cardiovascular health by reducing levels of molecules such as triglycerides and lipoproteins that drive disease. The biotech took both assets through midphase development. But, with a big cardiovascular outcome study next on the agenda, management has decided it can no longer back both horses. The end result is that plozasiran is in, while zodasiran is out. On a call with investors, Vincent Anzalone, head of investor relations at Arrowhead, framed the decision as being more about what’s right about plozasiran than what’s wrong with zodasiran. Plozasiran has generated compelling data in three settings, Anzalone said, and funding all of them could position Arrowhead to launch in progressively larger indications and stagger its commercial expansion. The fact plozasiran acts on triglycerides, while zodasiran is a LDL cholesterol drug, was another factor. Bruce Given, M.D., chief medical scientist at Arrowhead, said the cardiovascular disease drug market was different when the company was choosing whether to focus on APOC3, ANGPTL3 or both targets. “In the 2016, 2017 time frame, we didn't have PCSK9s. We didn't have the Regeneron antibody against ANGPTL3. We didn't have bempedoic acid. We really were pretty much having statins,” Given said. “Now there's actually a lot of drug availability over on the LDL side, a lot of competition for these patients.” In contrast, there is “still a relative desert with respect to the ability to really treat high triglycerides,” the Arrowhead executive said. Given sees plozasiran as a drug that can address unmet needs in a range of people, from symptomatic patients with pancreatitis through asymptomatic atherosclerotic individuals with mixed hyperlipidemia or severe hypertriglyceridemia. While Arrowhead is putting its own money behind plozasiran, the company hopes to find a partner for the now-deprioritized zodasiran. Given wants to see “somebody with the deep enough resources and large enough commercial apparatus that they could actually go compete in that LDL space” pick up the candidate and take it to market. “There are a lot of drugs over there, but they're not perfect. We do believe zodasiran in a perfect world, if you could snap your fingers and make it available, would be a big contribution in that space. But it's really beyond our capabilities at this time to prosecute it,” the executive said. The decision frees up Arrowhead to bet big on plozasiran. With a pivotal win in one setting positioning Arrowhead to bring plozasiran to market in 2025, the biotech is pushing ahead with other trials including a phase 3 cardiovascular outcomes study. The outcomes trial will mainly enroll people who have already had a cardiovascular event in the past but will also include a smaller primary prevention cohort.

AHAPhase 3

25 Mar 2024

·endpts.com

Esperion eyes new commercial push for cholesterol-lowering drugs after big FDA label expansion

Esperion has secured major FDA label expansions for its two cholesterol-lowering drugs, a regulatory milestone that it says opens up a much bigger market and “significantly reduces previously existing prescribing limitations.” Nexletol and Nexlizet are now approved to prevent heart attacks and cardiovascular procedures in both primary and secondary prevention patients, regardless of statin use. Both pills contain bempedoic acid, Esperion’s key asset, with one being a monotherapy and the other being a combination with another cholesterol-lowering drug, ezetimibe. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Drug Approval

100 Deals associated with Bempedoic acid

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External Link

KEGG	Wiki	ATC	Drug Bank
D10691	Bempedoic acid	C10AX15	DB11936

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cardiovascular Diseases	US	Esperion Therapeutics, Inc.	22 Mar 2024
Myocardial Infarction	US	Esperion Therapeutics, Inc.	22 Mar 2024
Primary Hyperlipidemia	US	Esperion Therapeutics, Inc.	22 Mar 2024
Dyslipidemias	EU	Daiichi Sankyo Europe GmbH	01 Apr 2020
Dyslipidemias	IS	Daiichi Sankyo Europe GmbH	01 Apr 2020
Dyslipidemias	LI	Daiichi Sankyo Europe GmbH	01 Apr 2020
Dyslipidemias	NO	Daiichi Sankyo Europe GmbH	01 Apr 2020
Primary hypercholesterolemia	EU	Daiichi Sankyo Europe GmbH	01 Apr 2020
Primary hypercholesterolemia	IS	Daiichi Sankyo Europe GmbH	01 Apr 2020
Primary hypercholesterolemia	LI	Daiichi Sankyo Europe GmbH	01 Apr 2020
Primary hypercholesterolemia	NO	Daiichi Sankyo Europe GmbH	01 Apr 2020
Atherosclerosis	US	Esperion Therapeutics, Inc.	21 Feb 2020
Heterozygous familial hypercholesterolemia	US	Esperion Therapeutics, Inc.	21 Feb 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyper LDL cholesterolaemia	Phase 3	JP	Otsuka Pharmaceutical Co., Ltd.	13 Feb 2023
Hyperlipidemias	Phase 3	US	Esperion Therapeutics, Inc.	23 Oct 2017
Drug-Related Side Effects and Adverse Reactions	Phase 3	US	Esperion Therapeutics, Inc.	16 Nov 2016
Drug-Related Side Effects and Adverse Reactions	Phase 3	CA	Esperion Therapeutics, Inc.	16 Nov 2016
Hypercholesterolemia	Phase 3	US	Esperion Therapeutics, Inc.	21 Jan 2016
Hypercholesterolemia	Phase 3	CA	Esperion Therapeutics, Inc.	21 Jan 2016
Hypercholesterolemia	Phase 3	DE	Esperion Therapeutics, Inc.	21 Jan 2016
Hypercholesterolemia	Phase 3	NL	Esperion Therapeutics, Inc.	21 Jan 2016
Hypercholesterolemia	Phase 3	PL	Esperion Therapeutics, Inc.	21 Jan 2016
Hypercholesterolemia	Phase 3	GB	Esperion Therapeutics, Inc.	21 Jan 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05683340 (Company_Website) Manual	Phase 3	Hypercholesterolemia	96	Bempedoic acid 180 mg	tyvxyflcck(favoezcxln) = kjkdlwtjgf fkfxeikiwz (iosnzxyvnj ) Met	Positive	20 May 2024
				Placebo	tyvxyflcck(favoezcxln) = kmvyrubbjm fkfxeikiwz (iosnzxyvnj ) Met
NCT04784442 (CTgov)	Phase 2	Hypercholesterolemia	188	Placebo	zkqpyffldg(vfafjpbwkb) = shwhulchyi uwyiszwntk (ykfdznoeef, ercjzdzdcj - sbstzdtorh) View more	-	04 Mar 2024
NCT02993406 (CLEAR Outcomes, CTgov)	Phase 3	Cardiovascular Diseases \| Drug-Related Side Effects and Adverse Reactions	13,970	Bempedoic acid 180 mg tablet (Bempedoic Acid 180 mg)	xjncxzwugm(nmhbaujiob) = yakowhxrho biyzvytjwa (xhyvctvila, xnikmtlamu - ncbrnglbqv) View more	-	03 Jan 2024
				Matching placebo tablet (Placebo Comparator)	xjncxzwugm(nmhbaujiob) = ebksbtuzfl biyzvytjwa (xhyvctvila, kkmdfmsucw - advelpppow) View more
MILOS (ESC2023)	Not Applicable	-	992	Bempedoic acid	rawvnalhdz(htytlopyls) = gwabnmposg xlsemojgyk (qwwteosdrd, (84.1)) View more	-	26 Aug 2023
				Bempedoic acid + ezetimibe	rawvnalhdz(htytlopyls) = cnfecdnhkg xlsemojgyk (qwwteosdrd, (123.6)) View more
NCT02993406 (Pubmed)	Phase 3	-	4,206	Bempedoic Acid	rkomwbzspf(gikpcextye): HR = 0.61 (95% CI, 0.39 - 0.98) View more	Positive	24 Jun 2023
				Placebo
NCT02178098 (CTgov)	-	Hypertension \| Hypercholesterolemia	143	Placebo	thyqitsamp(pbybkwuzih) = oweidpginw taevschlji (uwfhjqqeue, npxzbrbfcn - tnlvvzhskn) View more	-	04 Apr 2023
NCT02993406 (CLEAR Outcomes, Pubmed)	Phase 3	-	14,014	Bempedoic acid	ypwmiggeju(abjigtdvey) = 2.2% vs. 1.2% juzkfewlfm (swerwubjwq ) View more	Positive	04 Mar 2023
				Placebo
NCT02666664 (CLEAR Harmony, Pubmed)	Phase 3	Inflammation	817	Bempedoic acid 180 mg	dluaawkeuf(jbypuvbueo) = buamhjedod bavcktmkbg (defyxkvrsn, -10.1 to -6.6) View more	-	14 Feb 2023
NCT02993406 (CLEAR Outcomes, BusinessWire) Manual	Phase 3	-	14,014	Bempedoic acid	oloyzqxrge(xsxdjpughl) = significant relative risk reduction in major adverse CV events (MACE-4) in patients treated with 180 mg/day bempedoic acid compared to placebo (with no or very low statin background uzzgqitujx (zyjdvbyhrr )	Positive	08 Dec 2022
				Placebo
ESC2022	Not Applicable	Cardiovascular Diseases	-	Bempedoic acid	pvdoozmjti(ugwqwpqfjm) = hynagahuql uwrivtsdra (rjndnlyuic )	-	27 Aug 2022