egaptivon pegol (ARC1779)
/ Archemix
- LARVOL DELTA
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June 08, 2022
Development of a novel aptamer blocking the interaction between the VWF A1 domain and platelet GP Ib for the treatment of arterial thrombosis
(PubMed, Rinsho Ketsueki)
- "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. 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."
Journal • Cardiovascular • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis
May 13, 2021
[VIRTUAL] HALF-LIFE PROLONGATION OF VON WILLEBRAND FACTOR: A NEW THERAPEUTIC STRATEGY FOR HAEMOPHILIA A AND VON WILLEBRAND DISEASE
(EHA 2021)
- "However, intravenous infusion of the A1 domain blocking aptamer ARC1779 was also effective in patients with hyperactive VWF (VWD type IIb), and increased their plasma levels of VWF, FVIII and platelet counts pointing towards a potential hemostatic function, which may also be exploited...Methods Normal healthy volunteers received single ascending doses of the anti VWF aptamer BT200 ranging over 2.5 orders of magnitude from 0.18 mg to 48mg by subcutaneous injection or sc or iv...Conclusion This trial identified a novel mechanism of action for BT200: it decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or haemophilia A, which already confirms the expected effect sizes."
Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis
April 10, 2021
The Use of Fluorescently Labeled ARC1779 Aptamer for Assessing the Effect of H2O2 on von Willebrand Factor Exocytosis.
(PubMed, Biochemistry (Mosc))
- "The aim of our study was to determine the effect of H2O2 on 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 H2O2 for 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 H2O2 acts 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."
Journal • Immunology • Inflammation
November 03, 2020
Novel aptamer to von Willebrand factor A1 domain (TAGX-0004) shows total inhibition of thrombus formation superior to ARC1779 and comparable to caplacizumab.
(PubMed, Haematologica)
- "Surface plasmon resonance analysis of the binding sites of caplacizumab identified five amino acids in the VWF A1 domain (K1362, R1392, R1395, R1399, and K1406). These results suggested that TAGX-0004 possessed better pharmacological properties than caplacizumab in vitro and might be similarly promising for aTTP treatment."
Journal • Hematological Disorders • Thrombocytopenic Purpura • Thrombosis
July 03, 2020
Novel antiplatelet strategies targeting VWF and GPIb.
(PubMed, Platelets)
- "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."
Journal • Cardiovascular • Complement-mediated Rare Disorders • Thrombocytopenic Purpura
July 19, 2019
Short-Acting Anti-VWF (von Willebrand Factor) Aptamer Improves the Recovery, Survival, and Hemostatic Functions of Refrigerated Platelets.
(PubMed, Arterioscler Thromb Vasc Biol)
- "ARC1779 improves the post-transfusion recovery of refrigerated platelets and preserves the long-term hemostatic function of refrigerated platelets. These results suggest that a short-acting inhibitor of the platelet-VWF interaction may be a potential therapeutic option to improve refrigeration of platelets for transfusion treatment."
Journal
December 21, 2019
The Aptamer BT200 Blocks Von Willebrand Factor and Platelet Function in Blood of Stroke Patients
(ISC 2020)
- "Of 15 patients receiving clopidogrel with or without aspirin, only two had a prolonged collagen adenosine diphosphate closure time (CADP-CT) >123s, and only one patient had a ristocetin induced aggregation of <20U. BT200 effectively inhibits VWF activity and VWF-dependent platelet function in blood from patients with acute stroke. Results from this study proved useful for planning of the ongoing phase I and planned phase II trial."
Clinical
December 22, 2019
Novel aptamer to von Willebrand factor A1 domain (TAGX-0004) shows total inhibition of thrombus formation superior to ARC1779 and comparable to caplacizumab.
(PubMed, Haematologica)
- "Surface plasmon resonance analysis of the binding sites of caplacizumab identified five amino acids in the VWF A1 domain (K1362, R1392, R1395, R1399, and K1406). These results suggested that TAGX-0004 possessed better pharmacological properties than caplacizumab in vitro and might be similarly promising for aTTP treatment."
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