Delving into the Latest Updates on Eptifibatide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Eptifibatide (INN), Integrelin, Intrifiban

+ [8]

Target

GP IIb/IIIa

Mechanism

GP IIb/IIIa antagonists(Integrin alpha-IIb/beta-3 antagonists)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication

Angina, UnstableNon-St Elevated Myocardial InfarctionAcute Coronary Syndrome+ [1]

Inactive Indication

ST Elevation Myocardial Infarction

Originator Organization

Millennium Pharmaceuticals, Inc.

Active Organization

Accord Healthcare SLU

Jiangsu Hansoh Pharmaceutical Co., Ltd.GlaxoSmithKline (Ireland) Ltd.

+ [1]

Inactive Organization

GSK Plc

Merck Sharp & Dohme Corp.Schering-Plough Corp.

Drug Highest PhaseApproved

First Approval Date

US (18 May 1998),

Acute Coronary SyndromeMyocardial Infarction

Regulation-

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Structure

Molecular FormulaC35H49N11O9S2

InChIKeyCZKPOZZJODAYPZ-LROMGURASA-N

CAS Registry188627-80-7

Gene Sequence

Sequence Code 13855361

Source: *****

Author: Stiermaier, Thomas ; Eitel, Ingo ; Thiele, Holger ; Jurczyk, Dominik ; Mueller, Christian ; Desch, Steffen ; Fach, Andreas ; Hambrecht, Rainer ; Frerker, Christian ; Haaf, Philip ; Saraei, Roza ; Kurz, Thomas ; Joost, Alexander ; Wienbergen, Harm ; Marquetand, Christoph ; Schmidt, Tobias ; Fahrni, Gregor ; Allali, Abdelhakim

Abstract:

Background and Aims:

Glycoprotein (GP) IIb/IIIa inhibitors are recommended in acute myocardial infarction (AMI) for bailout treatment in case of angiographic microvascular obstruction (MVO), also termed no-reflow phenomenon, after percutaneous coronary intervention (PCI) with, however, lacking evidence (class IIa, level C).

Methods:

The investigator-initiated, international, multicentre REVERSE-FLOW trial randomized 120 patients with AMI and thrombolysis in myocardial infarction flow grade ≤ 2 after primary PCI to optimal medical therapy with or without GP IIb/IIIa inhibitor. The primary endpoint was infarct size [percentage of left ventricular (LV) mass assessed by cardiac magnetic resonance (CMR). Secondary endpoints included CMR-derived MVO and 30-day adverse clinical events. The trial is registered with ClinicalTrials.gov: NCT02739711.

Results:

The population was predominantly male (76.7%) with a median age of 66 years and ST-elevation myocardial infarction in 73.3% of patients. Clinical and angiographic characteristics were well balanced between the cohorts. Patients in the treatment group (n = 62) received eptifibatide (n = 41) or tirofiban (n = 21). Infarct size assessed by CMR imaging was similar in both study groups [25.4% of LV mass (%LV) vs. 25.2%LV; P = .386]. However, the number of patients with evidence of CMR-derived MVO (74.5% vs. 92.2%; P = .017) and the extent of MVO (2.1%LV vs. 3.4%LV; P = .025) were significantly reduced in the GP IIb/IIIa inhibitor group compared with controls. Thirty-day outcome showed an increased bleeding risk after GP IIb/IIIa inhibitor administration restricted to non–life-threatening bleedings (22.6% vs. 6.9%; P = .016) without differences in all-cause mortality (4.8% vs. 3.4%; P = .703).

Conclusions:

Bailout GP IIb/IIIa inhibition in AMI patients with angiographic MVO failed to reduce the primary endpoint infarct size but decreased CMR-derived MVO and led to an increase in non-fatal bleeding events.

05 Dec 2024·Microbiology Spectrum

It takes two to tango: Preserving daptomycin efficacy against daptomycin-resistant MRSA using daptomycin-phage co-therapy

Article

Author: Luedeke, Corrin E. ; Berti, Andrew D. ; Srivastava, Prakhar ; Hajjafar, Neeka ; Kebriaei, Razieh ; Madison, Casey L. ; Bayer, Arnold S. ; Steinert, Anja S. J.

ABSTRACT:

Daptomycin (DAP) is a cyclic lipopeptide antibiotic that targets the cell membrane and is commonly used for the treatment of multidrug-resistant Staphylococcus aureus infections, especially methicillin-resistant strains (MRSA). Emergence of DAP resistance during DAP therapy is increasingly reported; however, the mechanisms by which resistance occurs are diverse. Using phages in combination with antibiotics is of high interest to circumvent antibiotic resistance, due to their minimal side effects, accessibility, and synergistic effects with antibiotics. Here, we have investigated the relationship between DAP resistance and sensitivity to phage Sb-1 in a cohort of 14 clinical MRSA strains. This cohort consists of four isogenic pairs (a clinical DAP-susceptible parent and its isogenic DAP-resistant variant isolated during DAP treatment), and three DAP-susceptible/DAP-resistant strain pairs are created by traditional serial passaging in the presence of increasing DAP concentrations. Efficiency of plating (EOP) and bacteriophage plaque sizes were recorded, and synergy between the antibacterial agents was tested using the phage-antibiotic combination (PAC) checkerboard method. Plaque sizes and EOP significantly increased ( P = 0.019 and P = 0.008, respectively) as strains developed resistance to DAP. The PAC checkerboards conveyed less antagonistic patterns in DAP-resistant mutant strains compared with their DAP-susceptible counterparts. Antagonism was displayed in 71.4% (5/7) of the DAP-susceptible strains, while it was only present in 14.3% (1/7) of the DAP-resistant mutants. Transmission electron microscopy images showed significantly thicker cell walls in DAP-susceptible strains exposed to DAP monotherapy compared with either growth control or DAP-phage ( P = 0.0002 and 0.0007, respectively). These data indicate increased sensitivity to phage Sb-1 concurrent with the emergence of DAP resistance.

IMPORTANCE:

Multidrug-resistant Staphylococcus aureus is a threat to the health care system, especially cross-resistance between daptomycin (DAP) and glycopeptides through various mutations such as mprF (which is involved in the modification of membrane phospholipids in some bacteria) and yycG (part of a two-component regulatory system in bacteria that is important for regulating cell wall biosynthesis and other cellular processes) has been reported previously. Our current study shows adjunctive treatment with phage in DAP-resistant strains will lead to synergistic activity and larger phage plaque sizes, translating to elevated lytic performance. The addition of bacteriophage to standard-of-care antibiotic therapies for multidrug-resistant S. aureus infections has the potential to hinder, and possibly revert, resistance to antibiotics. Applying this strategy can potentially lead to the preservation of the current antibiotics. Verification of this salutary outcome in relevant ex vivo and in vivo models of endovascular infections is required to validate translatability.

01 Dec 2024·CURRENT MEDICAL RESEARCH AND OPINION

Treatment of cerebral venous thrombosis: a review

Review

Author: Khan, Maria ; Patel, Hamish ; Bell, Simon M. ; Borhani, Afshin ; Majid, Arshad ; Lunn, India ; Siddiqui, Fazeel M. ; Wasay, Mohammad ; Hameed, Sajid

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke. COVID-19 infection and vaccination have been associated with CVT. Fibrinolysis and mechanical thrombectomy may play an emerging role in management. We conducted a literature review summarizing current evidence on use of antiplatelets, anticoagulants, thrombolysis, and mechanical thrombectomy for the management of CVT and COVID-19 related CVT. This was achieved through a review of MEDLINE, PubMed, and Cochrane Reviews databases, performed using the search terms CVT AND "antiplatelets' aspirin", "ticagrelor", "clopidogrel", "eptifibatide", "Low-molecular-weight-heparin (LMWH)", "Unfractionated heparin (UH)", "warfarin", "DOACs", "rivaroxaban", "apixaban", "dabigatran", "fibrinolysis", "intra-sinus thrombolysis", "mechanical thrombectomy", and "craniectomy". We found that LMWH and UH are safe and effective for the management of acute CVT and should be considered first line. Warfarin may be used in the sub-acute phase for secondary prevention but has weak evidence. DOACs are potentially a safe warfarin alternative, but only warfarin is currently recommended in international guidelines. Antiplatelets show little evidence for the prevention or management of CVT, but studies are currently limited. COVID-19 related CVT is treated similarly to non-COVID-19 CVT; however, vaccine-related CVT is a newly recognised disease with a different pathophysiology and is treated with a combination of non-heparin anticoagulants, immunotherapy, and steroids. Decompressive craniectomy may be used to reduce intracranial pressure in life-threatening cases. There is a small body of evidence for endovascular therapy in complex cases but should be reserved for complex cases in specialist centres. This paper is of relevance to clinical practice since the safe and effective management of CVT is important to reduce the risk of disability.

9

News (Medical) associated with Eptifibatide

23 Sep 2024

·www.businesswire.com

Avenacy to Share Company’s Year One Progress at CPHI Milan 2024

SCHAUMBURG, Ill.--( BUSINESS WIRE )--Avenacy, a specialty pharmaceutical company focused on supplying critical medications, looks forward to celebrating its first year of growth and success since launching in October 2023. Backed by a robust global network of development and FDA-inspected contract manufacturing partners, Avenacy has already brought 13 injectable products to the U.S. market to address key gaps in the drug supply chain. “We are incredibly proud of the achievements and progress we have made at Avenacy since launching nearly a year ago as a trusted partner and provider of critical injectable medicines for the U.S. healthcare system,” said Jeff Yordon, Co-Founder and CEO of Avenacy. “We have acted swiftly and decisively to bring over a dozen medications to the U.S. market to help meet the needs of patients, strengthened our financial position with the addition of esteemed pharmaceutical investor and businessman, Dr. Patrick Soon-Shiong, and built out our infrastructure and leadership to support scaling up our business. As we look to usher in the next phase of growth for Avenacy, we will remain steadfast in our goal of enhancing patient care and enabling access to safe, high-quality essential medications.” Through a rigorous and optimized selection process, Avenacy has launched thirteen products in the U.S. market, including: Melphalan Hydrochloride for Injection Bivalirudin for Injection Fosaprepitant for Injection Fulvestrant Injection Furosemide for Injection Desmopressin Acetate for Injection Eptifibatide for Injection Magnesium Sulfate in Water for Injection Isoproterenol Hydrochloride Injection, USP Tranexamic Acid Injection, USP Prochlorperazine Edisylate Injection, USP Palonosetron Hydrochloride Injection, USP Metoclopramide Injection, USP The Company is well-positioned to continue expanding its differentiated portfolio to meet the needs of today’s dynamic drug supply chain while ensuring quality of care to patients. All of Avenacy’s products feature unique packaging and labeling designed to assist healthcare providers with accurate medication selection, thereby supporting a reduction in administration errors and improper dosing. The Company also utilizes ready-to-use formulations of essential medications to help address dosing inaccuracies, enhance patient safety, and streamline efficiency – all with the ultimate goal of improving patient care. Avenacy will be sharing its first year progress, differentiated business model, and diverse partner network at this year’s CPHI 2024 Conference, taking place in Milan from October 8-10. During this time, the Company will be hosting meetings with potential partners, customers, and investors, as it seeks to expand its global presence and portfolio of critical injectable medicines. About Avenacy Avenacy is a U.S.-based specialty pharmaceutical company focused on supplying critical injectable medications used to treat patients in various medically supervised settings, from acute care hospitals to outpatient clinics and physician offices. Through a rigorous and optimized selection process, the Company is building out a pipeline of high-quality FDA approved injectable products in order to ensure a resilient portfolio that can meet the needs of today’s dynamic drug supply chain. With an experienced team, commitment to quality and reliability, and product offerings intended to facilitate safe and efficient patient care, Avenacy strives to be a trusted partner for essential medications. Avenacy was launched in 2023 and is headquartered in Schaumburg, IL. For more information, please visit http://www.avenacy.com/ .

Executive Change

06 Sep 2024

·www.drugs.com

Adjunctive IV Argatroban, Eptifibatide Do Not Cut Disability After Stroke

FRIDAY, Sept. 6, 2024 -- Adjunctive treatment with intravenous argatroban or eptifibatide does not reduce poststroke disability among patients with acute ischemic stroke treated with intravenous thrombolysis within three hours after symptom onset, according to a study published in the Sept. 5 issue of the New England Journal of Medicine . Opeolu Adeoye, M.D., from Washington University in St. Louis, and colleagues conducted a phase 3, randomized, controlled clinical trial at 57 U.S. sites involving patients with acute ischemic stroke who had received intravenous thrombolysis within three hours after symptom onset. Participants received intravenous argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients) within 75 minutes after initiation of thrombolysis. The researchers found that at 90 days, the mean utility-weighted modified Rankin scale scores were 5.2 ± 3.7, 6.3 ± 3.2, and 6.8 ± 3.0 with argatroban, eptifibatide, and placebo, respectively. The posterior probabilities that argatroban was better than placebo and that eptifibatide was better than placebo were 0.002 and 0.041, respectively (posterior mean difference in utility-weighted modified Rankin scale score, −1.51 ± 0.51 and −0.50 ± 0.29, respectively). The three groups had a similar incidence of symptomatic intracranial hemorrhage (4, 3, and 2 percent, respectively). Mortality at 90 days was higher in the argatroban and eptifibatide groups versus the placebo group (24 and 12 percent, respectively, versus 8 percent). "We found no benefit of adjunctive intravenous argatroban or eptifibatide in patients with acute ischemic stroke treated with intravenous thrombolysis within three hours after symptom onset," the authors write. Several authors disclosed ties to the biopharmaceutical industry.

Clinical ResultPhase 3

29 Apr 2024

·www.biospace.com

Avenacy Announces Launch of Eptifibatide for Injection in the U.S. Market

SCHAUMBURG, Ill.--(BUSINESS WIRE)-- Avenacy, a specialty pharmaceutical company focused on supplying critical injectable medications, today announced it has launched Eptifibatide for Injection in the United States as a therapeutic equivalent generic for Integrilin® for Injection (Eptifibatide) approved by the U.S. Food and Drug Administration. Eptifibatide for Injection is indicated for use in acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). This press release features multimedia. View the full release here: (Photo: Business Wire) Avenacy’s Eptifibatide for Injection is available as a 75 mg/100 mL single-dose vial. In line with Avenacy’s mission to champion patient safety and streamline patient care, Eptifibatide for Injection will feature the Company’s highly differentiated packaging and labeling to support accurate medication selection. Avenacy will begin shipping Eptifibatide for Injection to wholesale partners this week. The Company is supported by a global network of development and FDA-approved cGMP-certified contract manufacturing partners. Eptifibatide for Injection had U.S. sales of approximately $8.3 million for the twelve months ending in June 2023.1 Approved Indications: Acute Coronary Syndrome (ACS) Eptifibatide injection is indicated to decrease the rate of a combined endpoint of death or new myocardial infarction in patients with ACS (unstable angina/non-ST-elevation myocardial infarction), including patients who are to be managed medically and those undergoing percutaneous coronary intervention. Percutaneous Coronary Intervention (PCI) Eptifibatide injection is indicated to decrease the rate of a combined endpoint of death, new MI, or need for urgent intervention in patients undergoing PCI, including those undergoing intracoronary stenting. Please see link for Full Prescribing Information. Integrilin® is a registered trademark of Merck. 1Source: IQVIA About Avenacy Avenacy is a U.S.-based specialty pharmaceutical company focused on supplying critical injectable medications used to treat patients in various medically supervised settings, from acute care hospitals to outpatient clinics and physician offices. Through a rigorous and optimized selection process, the Company is building out a pipeline of high-quality FDA approved injectable products in order to ensure a resilient portfolio that can meet the needs of today’s dynamic drug supply chain. With an experienced team, commitment to quality and reliability, and product offerings intended to facilitate safe and efficient patient care, Avenacy strives to be a trusted partner for essential medications. Avenacy was launched in 2023 and is headquartered in Schaumburg, IL. For more information, please visit .

Drug Approval

100 Deals associated with Eptifibatide

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External Link

KEGG	Wiki	ATC	Drug Bank
D06888	Eptifibatide	B01AC16	DB00063

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Angina, Unstable	US	Merck Sharp & Dohme Corp.	16 Jun 2003
Non-St Elevated Myocardial Infarction	US	Merck Sharp & Dohme Corp.	16 Jun 2003
Acute Coronary Syndrome	US	Merck Sharp & Dohme Corp.	18 May 1998
Myocardial Infarction	US	Merck Sharp & Dohme Corp.	18 May 1998

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
ST Elevation Myocardial Infarction	Phase 3	FR	GSK Plc	01 Oct 2006
ST Elevation Myocardial Infarction	Phase 3	DE	GSK Plc	01 Oct 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03735979 (phase 3 \| MOST, CTgov)	Phase 3	Acute Ischemic Stroke	514	Argatroban (Argatroban)	qrxnyvelrp(lsfxpepqbq) = etpkeqgfbs bgsjjdeymv (yytnkcjppv, fjkbbqfxbf - rfuixbgynp) View more	-	19 Nov 2024
				Eptifibatide (Eptifibatide)	qrxnyvelrp(lsfxpepqbq) = vyynnardgj bgsjjdeymv (yytnkcjppv, bwemkkrnqn - tjhgbuluxq) View more
NCT03735979 (MOST, Literature \| Pubmed \| N Engl J Med) Manual	Phase 3	Ischemic stroke Adjuvant	514	Argatroban	cbhwqxhtwo(lepkrpcvlg) = ewyimuyyfy wyvfugltfn (alkirunyii ) View more	Negative	04 Sep 2024
				Eptifibatide	cbhwqxhtwo(lepkrpcvlg) = ghrdbfzdch wyvfugltfn (alkirunyii ) View more
EHA2024	Not Applicable	Acute Coronary Syndrome	26	Eptifibatide	lkucuderms(ciolofcuqy) = 54% of patients experienced a platelet drop exceeding 50%, with a median post-exposure count of 76 × 10^9/L after a median duration of 36 hours. Ten percent of patients necessitated permanent eptifibatide cessation due to severe thrombocytopenia (lowest platelet count: 2 × 10^9). Treatment primarily involved a temporary hold of eptifibatide infusion in 90% of cases, with a minority receiving platelet transfusions; no patients received steroids or immunoglobulins. lhftrepoht (frbekhejns )	-	14 May 2024
ISC2024	Not Applicable	-	-	IA Eptifibatide	txgbvhcwbs(rxvnfuayug): OR = 0.592 (95% CI, 0.228 - 1.539), P-Value = 0.28	-	01 Feb 2024
				No IA Eptifibatide
NCT03370939 \| NCT03844594 (ANGEL-ACT, Pubmed \| Stroke)	Phase 3	Acute Ischemic Stroke	162	mechanical thrombectomy+Eptifibatide	cltqocfymz(apdsqhzcks) = bgjkcrmacm rguelrgtuk (jvzyaxbhbs ) View more	Positive	02 Feb 2022
				mechanical thrombectomy	cltqocfymz(apdsqhzcks) = dmsmyoqgzb rguelrgtuk (jvzyaxbhbs ) View more
ISC2022	Not Applicable	Ischemic stroke	236	Eptifibatide	qyqujrrwfo(yqbaptuqcv) = EPT during EVT was associated with a higher rate of PH-2 grade hemorrhages bobgptgwyb (qwfvkrxtle )	-	01 Feb 2022
				Eptifibatide (Control groups)
NCT02925923 (CTgov)	Phase 2	Angina, Unstable \| Acute Coronary Syndrome \| Acrocallosal Syndrome	100	Ticagrelor (Ticagrelor)	pdudfkcbbv(etmruqwbvl) = zisobzdgzd iwfjydtxwx (dciabnpbyn, uunwbmlvua - lybzoggxoo) View more	-	04 May 2020
				clopidogrel+Eptifibatide (Eptifibatide Bolus+Clopidogrel)	pdudfkcbbv(etmruqwbvl) = njvyqnidix iwfjydtxwx (dciabnpbyn, fbfuhoiulu - brrrfdicqx) View more
CLEAR-FDR (ISC2016)	Phase 2	Ischemic stroke	-	Full dose rt-PA plus eptifibatide	bkadyzfvxa(ghikloooas) = azieiwnjzn woagofotbk (frfnjlbdfu ) View more	-	01 Feb 2016
				rt-PA alone	bkadyzfvxa(ghikloooas) = vjujisawug woagofotbk (frfnjlbdfu ) View more
NCT01977456 (CLEAR-FDR, CTgov)	Phase 2	Brain Infarction \| Acute Ischemic Stroke	27	Eptifibatide	zfnplspeid(ozisorxdzi) = kiurmogsrj mqvelizdzu (uexiagihna, eqtjpjznur - gzbfbukrkm) View more	-	25 Nov 2015
NCT01977456 (CLEAR-FDR, Pubmed \| Stroke)	Phase 2	Acute Ischemic Stroke	27	Full-dose r-tPA plus eptifibatide	zwuqkyjxzb(kfjbdobtfd) = akzxqqozrt zialrirhod (pkqjnrtoob, 0.7% - 18%)	-	01 Sep 2015