Delving into the Latest Updates on Egaptivon pegol with Synapse

Overview

Basic Info

Drug Type

DNA aptamer

Synonyms

Egaptivon pegol (USAN)

Target

vWF

Action

inhibitors

Mechanism

vWF inhibitors(Von willebrand factor inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesCongenital Disorders+ [2]

Active Indication-

Inactive Indication

Brain InfarctionCarotid StenosisCongenital Thrombotic Thrombocytopenic Purpura+ [5]

Originator Organization

Archemix Corp.

Active Organization-

Inactive Organization

Archemix Corp.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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Sequence Code 271898487

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The purpose of this study is to determine, in patients undergoing carotid endarterectomy, the effect of ARC1779 Injection on the number of microembolic signals detected by transcranial Doppler immediately after surgery. This study will also evaluate the safety of ARC1779 Injection with respect to bleeding risk in patients in the peri-operative (during surgery) period.

Start Date01 Feb 2009

Sponsor / Collaborator

Archemix Corp.

[+1]

EUCTR2008-005246-23-GB

/ Not yet recruitingNot Applicable

A Study of the Effect of ARC1779 Injection on Cerebral Microembolism in PatientsUndergoing Carotid Endarterectomy

Start Date17 Dec 2008

Sponsor / Collaborator

Archemix Corp.

100 Clinical Results associated with Egaptivon pegol

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100 Translational Medicine associated with Egaptivon pegol

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100 Patents (Medical) associated with Egaptivon pegol

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23

Literatures (Medical) associated with Egaptivon pegol

01 Jan 2022·[Rinsho ketsueki] The Japanese journal of clinical hematology

[Development of a novel aptamer blocking the interaction between the VWF A1 domain and platelet GP Ib for the treatment of arterial thrombosis].

Article

Author: Harada, Kaori ; Matsumoto, Masanori

A DNA aptamer to the von Willebrand factor (VWF) A1 domain, TAGX-0004, inhibits the binding of VWF to platelets. Nucleic acid aptamers are single-stranded DNA or RNA molecule forming three-dimensional structures that are capable of specifically binding to proteins and are expected to contribute to alternative medicine. ARC1779, an aptamer targeting the VWF A1 domain, had been evaluated in a phase II clinical trial of patients with acquired thrombotic thrombocytopenic purpura (aTTP); however, its development was terminated. Caplacizumab, an anti-VWF A1 domain nanobody, is now increasingly employed as first-line therapy for the treatment of aTTP in Western countries. However, there have been reports regarding adverse bleeding events and the high cost of the treatment. In this study, the inhibitory effects of TAGX-0004 were compared with those of ARC1779 and caplacizumab on in vitro platelet aggregation and thrombus formation. TAGX-0004 had an excellent high affinity to the VWF A1 domain and superior efficacy, such as its potent inhibitory activity in in vitro platelet aggregation and thrombus formation. Therefore, it can potentially overcome the problems associated with caplacizumab and can be developed as a promising drug not only for aTTP treatment but also for the treatment of the various VWF-mediated thrombotic disorders.

01 Feb 2021·Biochemistry (Moscow)Q4 · BIOLOGY

The Use of Fluorescently Labeled ARC1779 Aptamer for Assessing the Effect of H2O2 on von Willebrand Factor Exocytosis

Q4 · BIOLOGY

Article

Author: Goncharov, Nikolay V ; Tsitrina, Aleksandra A ; Avdonin, Pavel V ; Avdonin, Piotr P ; Trufanov, Sergey K ; Rybakova, Elena Yu

AbstractHere, we propose a new approach for quantitative estimation of von Willebrand factor (vWF) exposed on the surface of endothelial cells (ECs) using the ARC1779 aptamer that interacts with the vWF A1 domain. To visualize complex formation between vWF and the aptamer, the latter was conjugated with the Cy5 fluorescent label. Cultured human umbilical vein endothelial cells (HUVEC) were stained with the ARC1779-Cy5 conjugate and imaged with a fluorescence microscope. The images were analyzed with the CellProfiler software. vWF released from the Weibel–Palade bodies was observed as bright dot-like structures of round and irregular shape, the number of which increased several times after HUVEC exposure to histamine or thrombin. Staining with ARC1779-Cy5 also revealed long filamentous vWF structures on the surface of activated HUVEC. vWF secretion by ECs is activated by the second messengers cAMP and Ca2+. There is evidence that hydrogen peroxide also acts as a second messenger in ECs. In addition, exogenous H2O2formed in leukocytes can enter ECs. The aim of our study was to determine the effect of H2O2on the vWF exposure at the surface of HUVEC using the proposed method. It was shown that hydrogen peroxide at concentration 100 µM, which is lower than the cytotoxicity threshold of H2O2for cultured HUVEC, increased several times the number of dot-like structures and total amount of vWF exposed on plasma membrane of HUVEC, which suggest that H2O2acts as a mediator that activates exocytosis of Weibel–Palade bodies and vWF secretion in the vascular endothelium during inflammation and upon elevated generation of endogenous reactive oxygen species in ECs.

02 Jan 2021·PlateletsQ3 · MEDICINE

Novel antiplatelet strategies targeting VWF and GPIb

Q3 · MEDICINE

Review

Author: Scully, Marie ; Prasannan, Nithya

Von Willebrand factor has a pivotal role in primary hemostasis. Its role in thrombotic microangiopathies (TMA), as well as cardiovascular disease, has been demonstrated. Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a life-threatening condition with a high mortality rate if untreated. Current management strategies comprise plasma exchange to remove autoantibodies and replenish ADAMTS13, along with immunosuppressive agents in immune TTP. This review focuses on novel antiplatelet strategies that target VWF and GPIb. The benefits of the nanobody caplacizumab in achieving faster normalization of platelet count, as well as reduced thromboembolic events were shown through TITAN and HERCULES trials, and these findings have been practice changing. The use of caplacizumab in patients with immune TTP (iTTP) has now become well established. Potential benefits of ARC1779 and N-acetylcysteine have also been shown on a small scale in iTTP, however these lack evidence through larger randomized controlled trials. Further therapies, some in early phase, others in clinical practice, target platelet aggregation within arteries and their utility is presented with cerebrovascular disorders.

100 Deals associated with Egaptivon pegol

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External Link

KEGG	Wiki	ATC	Drug Bank
D09892	-	-	DB05202

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Brain Infarction	Phase 2	United Kingdom	Archemix Corp.	01 Feb 2009
Carotid Stenosis	Phase 2	United States	Archemix Corp.	01 Feb 2009
Carotid Stenosis	Phase 2	United Kingdom	Archemix Corp.	01 Feb 2009
Intracranial Embolism	Phase 2	United States	Archemix Corp.	01 Feb 2009
Intracranial Embolism	Phase 2	United Kingdom	Archemix Corp.	01 Feb 2009
Congenital Thrombotic Thrombocytopenic Purpura	Phase 2	Austria	Archemix Corp.	01 Jan 2008
Purpura, Thrombotic Thrombocytopenic	Phase 2	Austria	Archemix Corp.	01 Jan 2008
Thrombotic Thrombocytopenic Purpura, Acquired	Phase 2	Austria	Archemix Corp.	01 Jan 2008
Von Willebrand Disease, Type 2	Phase 2	Austria	Archemix Corp.	01 Jan 2008
Von Willebrand Disease, Type 2	Phase 2	Austria	Archemix Corp.	01 Jan 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00742612 (Pubmed \| Stroke)	Phase 1	-	-	ARC1779	kmhmhpxjwq(kvwgtghnai) = rrxrkwcxzj flceyowkbg (evgxbqwwgl )	-	01 Aug 2011
NCT00742612 (Pubmed \| Stroke)	Phase 1	-	-	Placebo	kmhmhpxjwq(kvwgtghnai) = kmtpmqsyuq flceyowkbg (evgxbqwwgl )	-	01 Aug 2011
NCT00432770 (Pubmed \| Circulation)	Phase 1	-	47	ARC1779	svzwoymrwi(fdgkminwka) = hdkbezpikb ttszdrekqx (fokddpowhf ) View more	-	04 Dec 2007