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

Jiangsu Hansoh Pharmaceutical Co. Ltd.Accord Healthcare SLUGlaxoSmithKline (Ireland) Ltd.

+ [1]

Inactive Organization

Merck Sharp & Dohme Corp.Schering-Plough Corp.

GSK Plc

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: *****

This study delineates biobased foods. Curcumin (CRU) delivery modules were studied using pectin gel, Sesame oil (SO), and Kokum butter (KB) oleogel (OG). SB1, the control, has 10% OG. The pectin gel between 10 and 50% oleogel were emulsified by 2.5% tween 80. Surface, physical, chemical, and physiochemical properties of prepared bigels were examined. Microscopic studies show biphasic feature. With OG content, FTIR shows hydrogen bonding increasing and decreasing. XRD confirmed gel amorphousness. Stress relaxation indicated 10% control bigel had considerably less strength. Bigel impedance factors increased considerably with OG content, according to impedance profiles. The moisture study found that replacing hydro phase with OG phase in formulations reduced moisture content from 10 to 50%. Less CRU released from 20 to 50% bigel matrices than 10% during in vitro studies. Acidic pH hindered polymer relaxation, altering release behaviour. Overall, the bigels were studied and shown to regulate oral CRU administration.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10068-024-01559-3.

05 Sep 2024·New England Journal of Medicine

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke

Article

Author: Majjhoo, Aniel ; Adeoye, Opeolu ; Panagos, Peter ; Graves, Todd ; Pancioli, Arthur ; Ranasinghe, Tamra ; Streib, Christopher ; Vagal, Achala ; Huang, Josephine ; Barsan, William ; Barreto, Andrew D ; Derdeyn, Colin P ; Concha, Mauricio ; Berry, Scott ; Janis, Scott ; Sivakumar, Sanjeev ; Wintermark, Max ; Sabagha, Noor ; Gentile, Nina ; Jasne, Adam S ; Broderick, Joseph ; Khatri, Pooja ; Demel, Stacie ; Yoo, Albert J ; Davis, Iris ; Pizzella, Stephanie ; Bentho, Oladi ; Grotta, James C ; Elm, Jordan ; Wilson, Alastair ; Ingles, James ; Hoffman, Melissa ; Levine, Steven R

BACKGROUNDIntravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.METHODSWe conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization.RESULTSA total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%).CONCLUSIONSIn patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

27 Aug 2024·Blood Advances

An αIIbβ3 monoclonal antibody traps a semiextended conformation and allosterically inhibits large ligand binding

Article

Author: Coller, Barry S ; Coller, Barry S. ; Wang, Jialing ; Wang, Lu ; Walz, Thomas ; Li, Jihong

AbstractMonoclonal antibodies (mAbs) have provided valuable information regarding the structure and function of platelet αIIbβ3. Protein disulfide isomerase (PDI) has been implicated in αIIbβ3 activation and binds to thrombin-activated αIIbβ3. Using human platelets as the immunogen, we identified a new mAb (R21D10) that inhibits the binding of PDI to platelets activated with thrombin receptor–activating peptide (T6). R21D10 also partially inhibited T6-induced fibrinogen and PAC-1 binding to platelets, as well as T6- and adenosine 5'-diphosphate–induced platelet aggregation. Mutual competition experiments showed that R21D10 does not inhibit the binding of mAbs 10E5 (anti-αIIb cap domain) or 7E3 (anti-β3 β-I domain), and immunoblot studies indicated that R21D10 binds to β3. The dissociation of αIIbβ3 by EDTA had a minimal effect on R21D10 binding. Cryogenic electron microscopy of the αIIbβ3-R21D10 Fab complex revealed that R21D10 binds to the β3 integrin-epidermal growth factor 1 (I-EGF1) domain and traps an intermediate conformation of αIIbβ3 with semiextended leg domains. The binding of R21D10 produces a major structural change in the β3 I-EGF2 domain associated with a new interaction between the β3 I-EGF2 and αIIb thigh domains, which may prevent the swing-out motion of the β3 hybrid domain required for high-affinity ligand binding and protect αIIbβ3 from EDTA-induced dissociation. R21D10 partially reversed the ligand binding priming effect of eptifibatide, suggesting that it could convert the swung-out conformation into a semiextended conformation. We concluded that R21D10 inhibits ligand binding to αIIbβ3 via a unique allosteric mechanism, which may or may not be related to its inhibition of PDI binding.

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	IL	Hainan Poly Pharm. Co., Ltd.	08 Nov 2023
Non-St Elevated Myocardial Infarction	IL	Hainan Poly Pharm. Co., Ltd.	08 Nov 2023
Acute Coronary Syndrome	CN	Jiangsu Hansoh Pharmaceutical Co. Ltd.	30 Oct 2012
Myocardial Infarction	IS	GlaxoSmithKline (Ireland) Ltd.	01 Jul 1999
Myocardial Infarction	NO	GlaxoSmithKline (Ireland) Ltd.	01 Jul 1999
Myocardial Infarction	EU	GlaxoSmithKline (Ireland) Ltd.	01 Jul 1999
Myocardial Infarction	LI	GlaxoSmithKline (Ireland) Ltd.	01 Jul 1999

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
ST Elevation Myocardial Infarction	Phase 1	DE	GSK Plc	01 Oct 2006
ST Elevation Myocardial Infarction	Phase 1	FR	GSK Plc	01 Oct 2006
Myocardial Infarction	Phase 1	US	Merck Sharp & Dohme Corp.	18 May 1998
ST Elevation Myocardial Infarction	Preclinical	FR	GSK Plc	01 Oct 2006
ST Elevation Myocardial Infarction	Preclinical	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, Pubmed \| N Engl J Med)	Phase 3	Ischemic stroke	514	Argatroban	ryncclqwff(jqodxcldpe) = ytxojtwtpc gzuhvqpdnp (iwrdqstbhg )	Negative	05 Sep 2024
				Eptifibatide	ryncclqwff(jqodxcldpe) = gkkqylqhby gzuhvqpdnp (iwrdqstbhg )
NCT03735979 (MOST, Literature) Manual	Phase 3	Ischemic stroke Adjuvant	514	Argatroban	(vwjshpwcab) = notohsykbl ajuqicoamo (gfbirlfllp ) View more	Negative	04 Sep 2024
				Eptifibatide	(vwjshpwcab) = cixkneanwu ajuqicoamo (gfbirlfllp ) View more
EHA2024	Not Applicable	Acute Coronary Syndrome	26	Eptifibatide	(lxwpmlpusz) = 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. ddmjakfips (zqsqwsgylb )	-	14 May 2024
NCT03370939 \| NCT03844594 (ANGEL-ACT, Pubmed \| Cochrane Database Syst Rev)	Not Applicable	Acute Ischemic Stroke	162	mechanical thrombectomy+Eptifibatide	ptcvedhlvn(fzzstsnjie) = wjfczrgtco fllusqrriz (lhnpuwckwb ) View more	Positive	02 Feb 2022
				mechanical thrombectomy	ptcvedhlvn(fzzstsnjie) = ulpyvhrgrv fllusqrriz (lhnpuwckwb ) View more
ISC2022	Not Applicable	Ischemic stroke	236	Eptifibatide	hjsmbwefzw(qbjirffcik) = EPT during EVT was associated with a higher rate of PH-2 grade hemorrhages zixmeroeky (tdextukovk )	-	01 Feb 2022
				Eptifibatide (Control groups)
ESC2021	Not Applicable	Plaque, Atherosclerotic	-	Glenzocimab	jblhmooqiv(dbtmghmvgs) = xhvsxnzepm gmmeixzjcn (yqfslhbksz ) View more	-	28 Aug 2021
				Aspirin and ticagrelor	jblhmooqiv(dbtmghmvgs) = sjuhxbwnqk gmmeixzjcn (yqfslhbksz ) View more
NCT02925923 (CTgov)	Phase 2	Angina, Unstable \| Acute Coronary Syndrome \| Acrocallosal Syndrome	100	Ticagrelor (Ticagrelor)	zlmmysbajb(zadrdluoyg) = rfwwyhxzha yljoejgnle (wpsnwpltod, lbgurleybs - hjvozjcieb) View more	-	04 May 2020
				clopidogrel+Eptifibatide (Eptifibatide Bolus+Clopidogrel)	zlmmysbajb(zadrdluoyg) = vvhekhozfv yljoejgnle (wpsnwpltod, xaobktyexk - aqwgyzfvsn) View more
NCT01919723 (Pubmed \| J Am Heart Assoc) Manual	Phase 2	Acute Coronary Syndrome	70	Eptifibatide+Ticagrelor (group 1)	(edqvrkvttp) = nggxauoono ihuwtxscmj (nrzoscwbku, 0.43) View more	Positive	13 Jun 2017
				Eptifibatide+Ticagrelor (group 2)	(edqvrkvttp) = wnnhldzhnl ihuwtxscmj (nrzoscwbku, 1.0) View more
NCT01919723 (CTgov)	Phase 2	Acute Coronary Syndrome	70	Eptifibatide+Ticagrelor (Ticagrelor and Eptifibatide Bolus)	rigmmmbrdz(ykvxtgjgmd) = ngszwtplht xnshpbwvro (qnquetqtpe, ngftkteeft - otusivvrbz) View more	-	28 Feb 2017
				Eptifibatide+Ticagrelor (Ticagrelor & Eptifibatide Bolus+Infusion)	rigmmmbrdz(ykvxtgjgmd) = jqzqfwyvwo xnshpbwvro (qnquetqtpe, eypwflqifg - zugozrthaw) View more
CLEAR-FDR (ISC2016)	Phase 2	Ischemic stroke	-	Full dose rt-PA plus eptifibatide	tvczntxjlc(wiuaokpxfg) = peimivzqpd otyqtgpxue (nqbzjxdrfj ) View more	-	01 Feb 2016
				rt-PA alone	tvczntxjlc(wiuaokpxfg) = ykanwefnov otyqtgpxue (nqbzjxdrfj ) View more