Delving into the Latest Updates on Anacetrapib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Anacetrapib (JAN/USAN), MK-0859

Target

CETP

Mechanism

CETP inhibitors(Cholesteryl ester transfer protein inhibitors)

Therapeutic Areas

Cardiovascular DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

AtherosclerosisCoronary DiseaseDyslipidemias+ [9]

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization-

Inactive Organization

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLC

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

Structure

Molecular FormulaC30H25F10NO3

InChIKeyMZZLGJHLQGUVPN-HAWMADMCSA-N

CAS Registry875446-37-0

There are currently no studies evaluating the effect of anacetrapib on blood vessel function and stiffness of the arteries. The REVEAL-Vasc trial will assess whether anacetrapib, in addition to atorvastatin (LDL-C lowering drug) treatment, results in greater endothelial-dependent vascular function and aortic stiffness in patients with established cardiovascular disease, compared to adding placebo.
Participants will be asked to provide a blood sample and pulse Wave Velocity/Pulse Wave Analysis and Flow Mediated Dilation will be carried out to assess blood vessel function and stiffness of the arteries. REVEAL-Vasc is an investigator led sub-study of HPS3/TIMI 55: REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid modification): A large-scale, randomized placebo-controlled trial of the clinical effects of anacetrapib among people with established vascular disease (NCT01252953) which is coordinated by OXFORD CTSU.
No treatment will be received on this sub-study, therefore only participants who have been enrolled in HPS3/TIMI55 REVEAL in which participants received anacetrapib with atorvastatin or placebo will be considered for this trial.

Start Date01 Jan 2017

Sponsor / Collaborator

Cambridge University Hospitals NHS Foundation Trust

CTR20130983 / Completed

在中国健康受试者中进行的MK-0859单次给药和多次给药的药代动力学研究

[Translation] Single-dose and multiple-dose pharmacokinetic study of MK-0859 in healthy Chinese subjects

评估50-、 100-、200-mg MK-0859在中国患者中药代动力学特征

[Translation]

To evaluate the pharmacokinetic characteristics of 50-, 100-, and 200-mg MK-0859 in Chinese patients

Start Date30 May 2016

Sponsor / Collaborator

Merck Sharp & Dohme (China) Ltd.

[+1]

PER-004-14 / Unknown statusPhase 3

A WORLDWIDE, MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY TO ASSESS THE TOLERABILITY AND EFFICACY OF ANACETRAPIB WHEN ADDED TO ONGOING THERAPY WITH A STATIN IN PATIENTS WITH CORONARY HEART DISEASE (CHD) OR CHD RISK-EQUIVALENT DISEASE: EVALUATION OF ANACETRAPIB LEVELS IN PLASMA AND ADIPOSE TISSUE IN PATIENTS WHO WERE PREVIOUSLY TREATED WITH ANACETRAPIB IN THE PROTOCOL 019, DEFINE STUDY

Start Date14 May 2014

Sponsor / Collaborator-

100 Clinical Results associated with Anacetrapib

Login to view more data

100 Translational Medicine associated with Anacetrapib

Login to view more data

100 Patents (Medical) associated with Anacetrapib

Login to view more data

216

Literatures (Medical) associated with Anacetrapib

01 Nov 2023·Pharmacological research

The evolving role of cholesteryl ester transfer protein inhibition beyond cardiovascular disease

Review

Author: Dicklin, Mary R ; Mehta, Nehal ; Ditmarsch, Marc ; Kastelein, John J P ; Rensen, Patrick C N ; Dangas, Katerina

The main role of cholesteryl ester transfer protein (CETP) is the transfer of cholesteryl esters and triglycerides between high-density lipoprotein (HDL) particles and triglyceride-rich lipoprotein and low-density lipoprotein (LDL) particles. There is a long history of investigations regarding the inhibition of CETP as a target for reducing major adverse cardiovascular events. Initially, the potential effect on cardiovascular events of CETP inhibitors was hypothesized to be mediated by their ability to increase HDL cholesterol, but, based on evidence from anacetrapib and the newest CETP inhibitor, obicetrapib, it is now understood to be primarily due to reducing LDL cholesterol and apolipoprotein B. Nevertheless, evidence is also mounting that other roles of HDL, including its promotion of cholesterol efflux, as well as its apolipoprotein composition and anti-inflammatory, anti-oxidative, and anti-diabetic properties, may play important roles in several diseases beyond cardiovascular disease, including, but not limited to, Alzheimer's disease, diabetes, and sepsis. Furthermore, although Mendelian randomization analyses suggested that higher HDL cholesterol is associated with increased risk of age-related macular degeneration (AMD), excess risk of AMD was absent in all CETP inhibitor randomized controlled trial data comprising over 70,000 patients. In fact, certain HDL subclasses may, in contrast, be beneficial for treating the retinal cholesterol accumulation that occurs with AMD. This review describes the latest biological evidence regarding the relationship between HDL and CETP inhibition for Alzheimer's disease, type 2 diabetes mellitus, sepsis, and AMD.

03 Oct 2023·Journal of the American Heart Association

Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States

Article

Author: Landray, Sir Martin J ; Bowman, Louise ; Williams, Claire ; Lui, Juliana Nga Man ; Hopewell, Jemma C ; Mihaylova, Borislava ; Chen, Fang ; Sammons, Emily ; Keng, Mi Jun ; Gray, Alastair

Background:

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate‐ and longer‐term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and Results:

Data on demographic and clinical characteristics, health‐related quality of life (QoL: EuroQoL 5‐Dimension‐5‐Level), adverse events, and hospital admissions during the 4‐year follow‐up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (−0.067 [United Kingdom], −0.069 [US]), heart failure admission (−0.072 [United Kingdom], −0.103 [US]), incident cancer (−0.064 [United Kingdom], −0.068 [US]), and noncoronary revascularization (−0.071 [United Kingdom], −0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539).

Conclusions:

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost‐effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration:

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252953; https://www.Isrctn.com . Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu . Unique identifier: 2010‐023467‐18.

01 Apr 2023·Current atherosclerosis reports

Structure-based mechanism and inhibition of cholesteryl ester transfer protein

Review

Author: Wang, Jianjun ; Liu, Jianfang ; Xue, Han ; Ren, Gang ; Zhang, Meng

Abstract:

Purpose of Review:

Cholesteryl ester transfer proteins (CETP) regulate plasma cholesterol levels by transferring cholesteryl esters (CEs) among lipoproteins. Lipoprotein cholesterol levels correlate with the risk factors for atherosclerotic cardiovascular disease (ASCVD). This article reviews recent research on CETP structure, lipid transfer mechanism, and its inhibition.

Recent Findings:

Genetic deficiency in CETP is associated with a low plasma level of low-density lipoprotein cholesterol (LDL-C) and a profoundly elevated plasma level of high-density lipoprotein cholesterol (HDL-C), which correlates with a lower risk of atherosclerotic cardiovascular disease (ASCVD). However, a very high concentration of HDL-C also correlates with increased ASCVD mortality. Considering that the elevated CETP activity is a major determinant of the atherogenic dyslipidemia, i.e., pro-atherogenic reductions in HDL and LDL particle size, inhibition of CETP emerged as a promising pharmacological target during the past two decades. CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, anacetrapib and obicetrapib, were designed and evaluated in phase III clinical trials for the treatment of ASCVD or dyslipidemia. Although these inhibitors increase in plasma HDL-C levels and/or reduce LDL-C levels, the poor efficacy against ASCVD ended interest in CETP as an anti-ASCVD target. Nevertheless, interest in CETP and the molecular mechanism by which it inhibits CE transfer among lipoproteins persisted. Insights into the structural-based CETP-lipoprotein interactions can unravel CETP inhibition machinery, which can hopefully guide the design of more effective CETP inhibitors that combat ASCVD.

Summary:

Individual-molecule 3D structures of CETP bound to lipoproteins provide a model for understanding the mechanism by which CETP mediates lipid transfer and which in turn, guide the rational design of new anti-ASCVD therapeutics.

1

News (Medical) associated with Anacetrapib

14 Jan 2021

·www.biospace.com

NewAmsterdam Pharma Completes $196M (€160M) Series A Funding for Comprehensive Phase 3 Development Program

Jan. 14, 2021 11:00 UTC Founding investor Forbion joined by co-lead investors, Morningside Ventures and Ascendant BioCapital, and other leaders in global biopharmaceutical investment Funding will support initiation and finalization of Phase 3 development of obicetrapib, a potent ApoB and LDL-c lowering small molecule drug, intended for patients not well-controlled on statins NewAmsterdam Pharma welcomes Jason Dinges of Morningside and Gaurav Gupta, MD of Ascendant BioCapital to its board of directors NAARDEN, the Netherlands--(BUSINESS WIRE)-- NewAmsterdam Pharma (NAP), a clinical stage company focused on the research and development of transformative therapies for cardio-metabolic diseases, today announced completion of a $196M (€160M) Series A funding round. The financing will support the full Phase 3 development of its ApoB and LDL-c lowering small molecule drug, obicetrapib. The drug, a cholesteryl ester transfer protein (CETP) inhibitor, is being developed for patients who are not well-controlled on statins. Forbion, NAP’s founding investor, was joined by Morningside Ventures and Ascendant BioCapital as co-lead investors in the Series A financing. Also participating in this funding round were Kaiser Foundation Hospitals, BVF Partners L.P., Population Health Partners, LSP Dementia Fund, Peter Thiel, Janus Henderson Investors, Medpace, GL Capital, JVC Investment Partners, and Presight Capital. “This is an important milestone in the advancement of obicetrapib and the growth of NewAmsterdam Pharma,” said Michael Davidson, MD, chief executive officer of NewAmsterdam Pharma. “The tremendous support of our investors allows us to initiate a large, Phase 3 development program as we work to create a new option for the millions of high cardiovascular risks patients globally who, despite maximally tolerated statin therapy, require additional LDL-c lowering options.” “Effectively inhibiting CETP to reduce atherosclerotic risk in patients is something Dr. Davidson and I have been endeavoring to achieve in our field of research for more than two decades,” said John Kastelein, MD, PhD, FESC, chief scientific officer of NewAmsterdam Pharma. “Long term follow up from the 2017 REVEAL study validated CETP as a target to lower LDL-c and reduce major adverse cardiac events (MACE).1 We believe that in obicetrapib, based on clinical studies to date, we have a molecule which is well tolerated and has not shown any of the safety issues of previous CETP inhibitors. Furthermore, based on the surrogate endpoints of the REVEAL study, obicetrapib was shown to be more effective at lowering LDL-c at a 5 mg dose in comparison to a 100 mg dose of anacetrapib.” “We are very pleased to support the development of obicetrapib and contribute to the success of NAP,” said Jason Dinges of Morningside. “We believe that obicetrapib has a unique efficacy and safety pro will further demonstrate not only a potent LDL-c lowering ability but other key attributes which could potentially benefit the large and underserved number of patients at risk of cardiovascular disease. We have confidence in the deep expertise and proven track record of Dr. Davidson and Dr. Kastelein to deliver these results.” “Cardiovascular disease remains the leading cause of disability-adjusted life years globally, and tens of millions of patients struggle to reach LDL-c goals on current therapies, demonstrating a clear need for novel agents,” said Gaurav Gupta, MD of Ascendant BioCapital. “CETP-silencing mutations correspond to lower cardiovascular risk, and given the potent pharmacology demonstrated in the TULIP study2, we expect obicetrapib to become a significant part of the treatment paradigm for dyslipidemia globally.” Two Phase 2b clinical trials for obicetrapib are underway with targeted completion in Q2 2021. NAP is looking to initiate Phase 3 clinical trials in Q4 2021. About Obicetrapib Obicetrapib is a cholesteryl ester transfer protein (CETP) inhibitor which targets Apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-c) in the body. Millions of people globally have cannot achieve LDL-c goals despite maximally tolerated statin therapy.3 A Phase 2b study called TULIP, published in The Lancet, showed that obicetrapib significantly reduced the number of ApoB-containing particles that constitute LDL-c and was well tolerated in patients with mild dyslipidemia. The randomized, double-blind, placebo-controlled study tested the drug in 364 patients, to assess the safety, tolerability, and efficacy of the potential therapy. Two Phase 2b clinical trials for obicetrapib are underway with targeted completion in Q2 2021. NAP is working to initiate Phase 3 trials in Q4 2021. About NewAmsterdam Pharma Founded in 2019 by the venture capital firm Forbion and John Kastelein, NewAmsterdam Pharma is a privately held, clinical-stage company focused on the research and development of transformative therapies for cardiometabolic diseases. Its mission is to improve patient care in populations where traditional therapies are not tolerated or have been unsuccessful. In April 2020, NewAmsterdam acquired Dezima Pharma from Amgen, including all rights for obicetrapib (formerly AMG 899, now TA-8995) a selective cholesteryl ester transfer protein (CETP) inhibitor. The Company is investigating obicetrapib as the preferred ApoB and LDL-c lowering therapy for patients with ASCVD/FH on the maximally tolerated dose of statin therapy. NewAmsterdam Pharma is headquartered in Naarden, The Netherlands. For more information, please visit: 1 2 Hovingh GK, Kastelein JP, van Deventer SJH, Round P, Ford, J, Saleheen D, et. al. Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidemia (TULIP): a randomized, double-blind, placebo-controlled phase 2 trial. The Lancet 2015.386(9992): 452-460. DOI: (15)60158-1 3 Ray K et al. EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DAVINCI study, European Journal of Preventive Cardiology 2020 View source version on businesswire.com: Contacts Media and Investor Inquiries: NewAmsterdam Pharma McDougall Communications on behalf of New Amsterdam Pharma Elizabeth Harness, P: +1 585-435-7379, elizabeth@mcdougallpr.com Christopher Knospe, P: +1 716-440-5580, chris@mcdougallpr.com Source: NewAmsterdam Pharma View this news release online at:

Small molecular drug

100 Deals associated with Anacetrapib

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D08855	Anacetrapib	-	DB06630

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
HoFM	Phase 3	-	Merck Sharp & Dohme Corp.	01 Jun 2013
Familial HDL Deficiency	Phase 3	-	Merck Sharp & Dohme Corp.	06 Nov 2012
Hypercholesterolemia	Phase 3	-	Merck Sharp & Dohme Corp.	06 Nov 2012
Heterozygous familial hypercholesterolemia	Phase 3	-	Merck Sharp & Dohme Corp.	03 Feb 2012
Hyperlipoproteinemia Type II	Phase 3	-	Merck Sharp & Dohme Corp.	03 Feb 2012
Coronary Disease	Phase 3	-	Merck Sharp & Dohme LLC	24 Mar 2008
Atherosclerosis	Phase 3	GB	Merck Sharp & Dohme Corp.	31 May 2006
Dyslipidemias	Phase 3	US	Merck Sharp & Dohme Corp.	31 May 2006
Dyslipidemias	Phase 3	CN	Merck Sharp & Dohme Corp.	31 May 2006
Dyslipidemias	Phase 3	CA	Merck Sharp & Dohme Corp.	31 May 2006

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01252953 (REVEAL, Pubmed \| Eur Heart J)	Phase 3	Atherosclerosis	30,449	Anacetrapib 100mg	wdtiyemswp(hjxoxiohag): proportional reduction = 9 (95% CI, 3 - 15), P-Value = 0.004	-	15 Dec 2021
				Placebo
NCT01524289 (REALIZE \| 0859-020 \| MK-0859-020, CTgov)	Phase 3	Heterozygous familial hypercholesterolemia \| Hyperlipoproteinemia Type II	306	Placebo	xoyyuytlkr(hberkrlqeq) = sepipkbubp ynqtbyhaqm (zrhtlgtkef, asqwpcyakj - evswhinmso) View more	-	28 Aug 2019
NCT01252953 (REVEAL, CTgov)	Phase 3	Atherosclerosis	30,449	Anacetrapib (Anacetrapib)	cyhpebsthh(xzkqutcldo) = msfompwuzt msukxvforz (zxnzlzjmon, xmxnexayuz - stnavuicdq) View more	-	04 May 2018
				Placebo anacetrapib (Placebo Anacetrapib)	cyhpebsthh(xzkqutcldo) = jtscfemqce msukxvforz (zxnzlzjmon, bskoyerrtq - tzzhxyotpp) View more
NCT01252953 (REVEAL, Pubmed \| Br Dent J) Manual	Phase 3	Atherosclerosis	30,449	Anacetrapib	xclfyxdxok(mymmisqwha) = vivnugrcsk obaflzsfxd (cizsboxfxl )	Positive	28 Sep 2017
				Placebo	xclfyxdxok(mymmisqwha) = hpuzlbgegv obaflzsfxd (cizsboxfxl )
NCT00990808 (0859-026, Pubmed \| Arterioscler Thromb Vasc Biol)	Phase 1	Hypercholesterolemia	39	Anacetrapib	qhvudwiaiu(suakgkeqyh) = odyehmjpit gxuuekugqn (zpevrdwwvf )	-	01 Sep 2017
NCT01524289 (ESC2017)	Phase 3	Heterozygous familial hypercholesterolemia LDLR \| APOB \| PCSK9	306	Anacetrapib 100 mg	sshjaylixm(itsxqngmtk) = pdijqodpry rhyonfpmfr (jungkuhprp )	-	26 Aug 2017
NCT01860729 (MK-0859-022, Pubmed \| Am J Cardiol) Manual	Phase 3	Hypercholesterolemia	583	ongoing therapy with statin ± other lipid-modifying therapies+Anacetrapib	ezmmdohrdt(alkvongcgt) = There were no clinically meaningful differences between the anacetrapib and placebo groups in the % patients who discontinued drug due to an adverse event or in abnormalities in liver enzymes, creatine kinase, blood pressure, electrolytes, or adjudicated cardiovascular events. xakwywycep (bveaafxink ) View more	Positive	15 Aug 2017
				ongoing therapy with statin ± other lipid-modifying therapies+Placebo
NCT01760460 (Pubmed \| Atherosclerosis) Manual	Phase 3	Dyslipidemias	307	anacetrapib	hczjwosgab(zekiihjllu) = nybdscqlhq thpkdibssu (xcmibvkpfi ) View more	Positive	01 Jun 2017
				Placebo	-
NCT01824238 (Pubmed \| Atherosclerosis) Manual	Phase 3	Heterozygous familial hypercholesterolemia	68	anacetrapib	hacyzictqt(fctedjsleg) = There were no differences between the groups in the proportion of patients who discontinued drug due to an adverse event or abnormalities in liver enzymes, creatinine kinase, blood pressure, electrolytes or adjudicated cardiovascular events. qfofxpdmbv (ppjbkyqfqw ) View more	Positive	01 Jun 2016
				Placebo
NCT01524289 (REALIZE, Pubmed \| Lancet) Manual	Phase 3	Heterozygous familial hypercholesterolemia	306	Anacetrapib	eiyfhranzf(zfresoazfr) = pffsfksvon bvvbmgcarc (urpwltopzi ) View more	Positive	30 May 2015
				Placebo	eiyfhranzf(zfresoazfr) = hjyetwtour bvvbmgcarc (urpwltopzi ) View more