Study of the therapeutic effect of the combination of altplas and ibtifibatide (integrilin) in comparison with altplas (r-TPA) alone, in the treatment of acute ischemic stroke

Start Date21 Apr 2021

Sponsor / Collaborator

Hamedan University of Medical Sciences

IRCT20200318046810N1 / CompletedNot ApplicableIIT

Assessment of Clopidogrel plus Eptifibatide versus Ticagrelor Treatment for No-reflow in patients with acute ST-Elevation MI referring for Primary Percutaneous coronary Intervention

Start Date20 May 2020

Sponsor / Collaborator

Tehran University of Medical Sciences

100 Clinical Results associated with Eptifibatide

100 Translational Medicine associated with Eptifibatide

100 Patents (Medical) associated with Eptifibatide

1,193

Literatures (Medical) associated with Eptifibatide

01 Jan 2024·JHEP reports : innovation in hepatology

Adenosine A2a receptor inhibition increases the anti-tumor efficacy of anti-PD1 treatment in murine hepatobiliary cancers

Article

Author: Greten, Tim F ; Benmebarek, Mohamed-Reda ; Xie, Changqing ; Myojin, Yuta ; Bauer, Kylynda C ; McVey, John C ; Ma, Chi ; Wabitsch, Simon ; Fu, Claude ; Ruf, Benjamin ; Green, Benjamin L ; McCallen, Justin D

Backgrounds & Aims:

The efficacy of immune checkpoint inhibitor (ICI) therapy for liver cancer remains limited. As the hypoxic liver environment regulates adenosine signaling, we tested the efficacy of adenosine A2a receptor (A2aR) inhibition in combination with ICI treatment in murine models of liver cancer.

Methods:

RNA expression related to the adenosine pathway was analyzed from public databases. Peripheral blood mononuclear cells of 13 patients with hepatocellular carcinoma (HCC) were examined by flow cytometry. The following murine cell lines were used: SB-1, RIL175, and Hep55.1c (liver cancer), CT26 (colon cancer), and B16-F10 (melanoma). C57BL/6 and BALB/c mice were used for orthotopic tumor models and were treated with SCH58261, an A2aR inhibitor, in combination with anti-PD1 therapy.

Results:

RNA expression of ADORA2A in tumor tissues derived from patients with HCC was higher than in tissues from other cancer types. A2aR⁺ T cells in peripheral blood from patients with HCC were highly proliferative after immunotherapy. Likewise, in an orthotopic murine model, A2aR expression on T cells increased following anti-PD1 treatment, and the expression of A2aR on T cells increased more in tumor-bearing mice compared with tumor-free mice. The combination of SCH58261 and anti-PD1 led to activation of T cells and reductions in tumor size in orthotopic liver cancer models. In contrast, SCH58261 monotherapy was ineffective in orthotopic liver cancer models and the combination was ineffective in the subcutaneous tumor models tested. CD4⁺ T-cell depletion attenuated the efficacy of the combination therapy.

Conclusion:

A2aR inhibition and anti-PD1 therapy had a synergistic anti-tumor effect in murine liver cancer models.

Impact and implications:

Adenosine A2a receptor (A2aR)-expressing T cells in the liver increased in tumor-bearing mice and after anti-PD1 treatment. The combination of an A2aR inhibitor and anti-PD1 treatment had potent anti-tumor effects in two murine models of orthotopic liver cancer. Adenosine A2a receptor blockade promotes immunotherapy efficacy in murine models, highlighting putative clinical benefits for advanced stage liver cancer patients.

19 Dec 2023·Journal of the American Heart Association

Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s)

Review

Author: van 't Hof, Arnoud W J ; Ten Berg, Jurriën M ; Kereiakes, Dean J ; Coller, Barry S ; Rikken, Sem A O F

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbβ3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000–100 000 platelets/μL), to severe (20 000 to <50 000/μL), to profound (<20 000/μL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin‐induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab‐associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbβ3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune‐mediated, with antibodies recognizing the αIIbβ3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second‐generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI‐associated thrombocytopenia.

01 Dec 2023·Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

Low dose intravenous cangrelor versus glycoprotein IIb/IIIa inhibitors in endovascular treatment of tandem lesions

Article

Author: Zaidi, Syed ; Farooqui, Mudassir ; Malik, Amer M ; Jovin, Tudor ; Rodriguez-Calienes, Aaron ; Divani, Afshin A ; Malaga, Marco ; Abraham, Michael ; Linares, Guillermo ; Janjua, Nazli ; Siegler, James E ; Yoo, Albert ; Ribo, Marc ; Sheth, Sunil ; Guerrero, Waldo R ; Galecio-Castillo, Milagros ; Ortega-Gutierrez, Santiago ; Vivanco-Suarez, Juan ; Jumaa, Mouhammad A ; Petersen, Nils ; Zevallos, Cynthia ; Fifi, Johanna ; Quispe-Orozco, Darko ; Dawod, Giana ; Hassan, Ameer E ; Oliver, Marion ; Nguyen, Thanh

OBJECTIVES:

Intravenous (IV) periprocedural antiplatelet therapy (APT) for patients undergoing acute carotid stenting during mechanical thrombectomy (MT) is not fully investigated. We aimed to compare the safety profile of IV low dose cangrelor versus IV glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors in patients with acute tandem lesions (TLs).

MATERIALS AND METHODS:

We retrospectively identified all cases of periprocedural administration of IV cangrelor or GP-IIb/IIIa inhibitors during acute TLs intervention from a multicenter collaboration. Patients were divided in two groups according to the IV APT regimen at the time of MT procedure: 1) cangrelor and 2) GP-IIb/IIIa inhibitors (tirofiban and eptifibatide). Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH), parenchymal hematoma type 1 and 2 (PH1-PH2), and hemorrhagic infarction type 1 and 2 (HI1-HI2).

RESULTS:

Sixty-three patients received IV APT during MT, 30 were in the cangrelor group, and 33 were in the GP-IIb/IIIa inhibitors group. There were no significant differences in the rates of sICH (3.3% vs. 12.1%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), HI1-HI2 (21.4% vs 42.4%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), and PH1-PH2 (17.9% vs. 12.1%, aOR=1.63, 95%CI 0.29-9.83, p=0.577) between both treatment groups. However, there was a trend toward reduced hemorrhage rates with cangrelor. Cangrelor was associated with increased odds of complete reperfusion (aOR=5.86; 95%CI 1.57-26.62;p=0.013).

CONCLUSIONS:

In this retrospective non-randomized cohort study, our findings suggest that low dose cangrelor has similar safety and increased rate of complete reperfusion compared to IV GP-IIb/IIIa inhibitors. Further prospective studies are warranted to confirm this association.

News (Medical) associated with Eptifibatide

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

17 Jul 2023

·www.biospace.com

Elektrofi Appoints Victoria Sluzky as Chief Technology Officer to Drive Innovation and Technical Excellence

BOSTON, July 17, 2023 (GLOBE NEWSWIRE) -- Today Elektrofi, a biopharmaceutical formulation technology company focused on leveraging strategic partnerships to revolutionize the delivery of biologic therapies, appointed Victoria Sluzky as Chief Technology Officer (CTO). Victoria brings more than 30 years of healthcare and biotechnology experience to Elektrofi. This strategic addition to the executive leadership team reflects Elektrofi's commitment to transforming the patient experience by formulating biologic therapies that can be delivered subcutaneously to patients when and where they need them, in seconds. Previously having served in a senior advisor role, as CTO, Victoria will be responsible for Elektrofi’s pharmaceutical development process including process development, formulation, analytics, and innovation. She will also oversee the company’s Chemical, Manufacturing, and Controls (CMC) groups, Regulatory, and related processes in support of advancing the Company’s clinical programs. “We are thrilled for Vikki to have joined our team in this newly created and business critical role,” said Chase Coffman, Ph.D., Chief Executive Officer, Elektrofi. “Throughout her career she has demonstrated exceptional skills in harnessing cutting-edge technologies, driving efficiency, and delivering impactful results. As we continue to scale our clinical programs and broaden our partnering strategy, I’m confident that her strategic leadership and operational expertise will ensure the highest level of scientific rigor and regulatory compliance across all operations.” Specializing in gene therapy and biologics manufacturing, Victoria has contributed to the approval of nine commercial products including Aldurazyme®, Brineura®, Integrilin®, Kuvan®, Naglazyme®, Palynziq®, Roctavian™, Vimizim®, and Voxzogo®. Prior to joining Elektrofi, she served as Senior Vice President of Technical Development for BioMarin Pharmaceutical and held notable positions at Scios, COR Therapeutics, and Onyx Pharmaceuticals. Victoria has a successful track record of building pre-clinical and clinical development programs ranging from small molecules and biologics to gene therapy drug candidates. Victoria holds a Ph.D. in Chemical Engineering from Massachusetts Institute of Technology and a Bachelor of Science in Chemical Engineering from Stanford University. She serves as a Fellow of American Institute of Medical and Biological Engineers, a non-profit organization headquartered in Washington, D.C., representing the most accomplished individuals in the fields of medical and biological engineering. "I am honored to work alongside talented Elektrofi colleagues as we leverage our first of its kind microparticle platform technology to achieve results and outcomes that have yet to be realized by anyone in the industry,” said Sluzky. “I look forward to leveraging my experience and passion for innovation to drive technical excellence and contribute to the remarkable work already being done at Elektrofi.” About Elektrofi Elektrofi is a biopharmaceutical formulation technology company that is revolutionizing the delivery of biologic therapies by giving patients the ability to control how they want to receive and benefit from life-changing medicines. Our breakthrough ultra-high concentration microparticle technology platform resolves the limitations associated with intravenously biologic therapies by enabling convenient at-home subcutaneous self-administration. With a focus on monoclonal antibodies, therapeutic proteins, and other large molecule drugs, we create, develop, and commercialize subcutaneous biologic therapies in collaboration with strategic partners. We believe a patient-centered healthcare approach can lead to a healthier world. We are headquartered in Boston and innovate globally. To learn more, visit Elektrofi.com or follow us on LinkedIn. Company Contact Paulette Gangemi Chief Human Resources Officer, Elektrofi media@elektrofi.com

Executive Change

30 Mar 2023

·endpts.com

Manufacturing roundup: Catalent to produce low-cost version of naloxone; CSL opens R&D site

Catalent will be manufacturing a low-cost version of the opioid overdose treatment naloxone as part of a contract with Harm Reduction Therapeutics. Catalent plans to manufacture the treatment at its facility in Morrisville, NC. No financial details on the deal were disclosed. Harm Reduction was granted priority review status for the NDA on its spray last year. The company has been working on a naloxone product since 2017. It is anticipating approval in July of this year and a US launch in early 2024. “This agreement marks a major milestone for Harm Reduction Therapeutics and is also a significant step forward in tackling a major public health issue in this country,” said Carla Vozone, VP of inhalation strategy at Catalent, in a release . CSL is opening a new 140,000-square-foot R&D center in Waltham, MA. The new site will include 54,000 square feet of lab space and will serve as the hub for CSL’s current and future vaccine design. CSL already has several locations across the US as well as Australia, Germany, the Netherlands and Switzerland. An Indian-based manufacturer of cough syrup, Marion Biotech which had allegedly led to deaths in Uzbekistan, had its license revoked by the local government. According to a report from the BBC, authorities in the Indian state of Uttar Pradesh canceled the license of Marion Biotech, stopping it from further manufacturing activities. In January, the WHO, along with the Uzbekistan Ministry of Health, issued an alert for several batches of cough syrups made by Marion after having found levels of diethylene glycol or ethylene glycol in them. The US branch of the Chinese CDMO PharmaBlock has opened a new R&D facility in the Philadelphia suburb of West Chester, PA. The new 30,000-square-foot facility includes research labs, clean rooms, manufacturing suites and analytical labs. The CDMO is also planning to manufacture active pharmaceutical ingredients in West Chester by 2024. “This state-of-the-art facility will enable us to provide our clients with the highest quality research and development solutions, and we look forward to continuing to innovate and advance,” said Jing Li, president of PharmaBlock (USA), in a release . PharmaBlock entered the US market in 2012 with a sales office in the Bay Area and eventually established an R&D facility in Hatfield, PA. Thermo Fisher and biotech Arsenal Biosciences will be entering into a collaboration to develop and produce autologous T cells for cancer treatment. Arsenal recently advanced its lead candidate, a T cell therapy for ovarian cancer, into clinical manufacturing and is working with Thermo Fisher’s line of products for cell therapy production. However, no other details on the partnership were disclosed. Thermo Fisher and Arsenal began working together in 2020. The Canadian specialty pharma outfit Juno Pharmaceuticals has received approval from Health Canada to import eptifibatide solution and has secured a six-month supply. According to a company release, the drug is used for patients with types of acute coronary symptoms to help prevent blood clots. This is used when patients undergo interventions, including stenting. However, the drug has been in limited supply since October 2022. Juno is centered on sourcing and importing medications that are having shortages in Canada and bringing them in. “Preventing future shortages will require encouraging global players to bring their products to the Canadian market. As we look to the future, investing in domestic production and bolstering bricks and mortar manufacturing on Canadian soil should be a priority,” said Juno CEO Mark Mantel in a release .

VaccineCell TherapyDrug ApprovalPriority Review

100 Deals associated with Eptifibatide

External Link

KEGG	Wiki	ATC	Drug Bank
D06888	Eptifibatide	B01AC16	DB00063

R&D Status

Approved

10 top approved records.

to view more data

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.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
ST Elevation Myocardial Infarction	Phase 2	US	Schering-Plough Corp.	01 Nov 2007

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EHA2024	Not Applicable	Acute Coronary Syndrome	26	Eptifibatide	vecuftfjri(tkwnvxrsgk) = 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. ltivooeuyp (bzoyxupyjs )	-	14 May 2024
NCT03370939 \| NCT03844594 (ANGEL-ACT, Pubmed \| Stroke)	Not Applicable	Acute Ischemic Stroke	162	mechanical thrombectomy+Eptifibatide	ipmydwzhjx(tdwclyewam) = uelozfcnwi yykugiedgd (dsoxshnmxv ) View more	Positive	02 Feb 2022
				mechanical thrombectomy	ipmydwzhjx(tdwclyewam) = uwdjpmdcvq yykugiedgd (dsoxshnmxv ) View more
ISC2022	Not Applicable	Ischemic stroke	236	Eptifibatide	writqrynsn(mgoahfrkwt) = EPT during EVT was associated with a higher rate of PH-2 grade hemorrhages tktazrspcq (aejcgcxagb )	-	01 Feb 2022
				Eptifibatide (Control groups)
NCT02925923 (CTgov)	Phase 2	Angina, Unstable \| Acute Coronary Syndrome \| Acrocallosal Syndrome	100	Ticagrelor (Ticagrelor)	mntunochrs(sspxnxkpmu) = knmhcivwqf bofsrhnkyg (ftnzwpngrh, ouftzbfsus - vjasdenjig) View more	-	04 May 2020
				clopidogrel+Eptifibatide (Eptifibatide Bolus+Clopidogrel)	mntunochrs(sspxnxkpmu) = lworikgpya bofsrhnkyg (ftnzwpngrh, guvzxvotyj - nhletfatjb) View more
CLEAR-FDR (ISC2016)	Phase 2	Ischemic stroke	-	Full dose rt-PA plus eptifibatide	ctthcyvgml(synwakmvwp) = aquvnqlmyo ybujvjxxkj (nfsanotzga ) View more	-	01 Feb 2016
				rt-PA alone	ctthcyvgml(synwakmvwp) = oxofnykecl ybujvjxxkj (nfsanotzga ) View more
NCT01977456 (CLEAR-FDR, CTgov)	Phase 2	Brain Infarction \| Acute Ischemic Stroke	27	Eptifibatide	drfgpxofta(lvonrcylzb) = dionnmkzfi qixyqavucx (pintdqetdu, rcoikbryoq - nssovtalqo) View more	-	25 Nov 2015
NCT01977456 (CLEAR-FDR, Pubmed \| Stroke)	Phase 2	Acute Ischemic Stroke	27	Full-dose r-tPA plus eptifibatide	sawxzkskru(qcncgoauxv) = supkiikknv dpxstwawcq (txctnuuork, 0.7% - 18%)	-	01 Sep 2015
NCT00894803 (CLEAR-ER, CTgov)	Phase 2	Brain Infarction \| Acute Ischemic Stroke	126	rt-PA (Rt-PA Only)	pcfetxnrid(nwvwbgxgjt) = sgkswqthuf zregmdqaie (khqwirtuie, mlxprrdmsm - djyiktnjuk) View more	-	17 Mar 2014
				rt-PA+Eptifibatide (Rt-PA and Eptifibatide)	pcfetxnrid(nwvwbgxgjt) = frlasanadj zregmdqaie (khqwirtuie, jxcyvuifln - xxehxtzsyr) View more
NCT01863134 (CTgov)	Phase 4	Non-St Elevated Myocardial Infarction \| Non ST segment elevation acute coronary syndrome	140	Placebo (Placebo)	wrzqjgiujb(dbcwzdwyfc) = wartdvtvzx liztnelfcm (tpqvdthfzm, qxiagwfivz - snphkpqyej) View more	-	31 Oct 2013
				Eptifibatide (Eptifibatide)	wrzqjgiujb(dbcwzdwyfc) = vtwzbvurpv liztnelfcm (tpqvdthfzm, xtmjnnspzg - paknfmsjci) View more
NCT00089895 (EARLY ACS \| P03684, Pubmed \| Am Heart J)	Phase 3	Acute Coronary Syndrome	9,406	Eptifibatide (Women)	rylxzlkdtl(wlmazrfocl): odds ratio = 5.8 (95% CI, 3.9 - 8.8)	-	01 Oct 2013
				Eptifibatide (Men)

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis