Delving into the Latest Updates on Rondaptivon Pegol with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

vWF

Action

inhibitors

Mechanism

vWF inhibitors(Von willebrand factor inhibitors)

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication

Hemophilia AVon Willebrand Disease, Type 2Von Willebrand Disease, Type 1+ [1]

Inactive Indication

AtherosclerosisIntracranial ArteriosclerosisStroke

Originator Organization

Band Therapeutics LLC

Active Organization

Band Therapeutics LLC

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 452969911

Source: *****

BT200 is a PEGylated aptamer that binds to the A1 domain of human von Willebrand factor (VWF). At low doses, BT200 blocks the clearance of VWF antigen (VWF Ag) from the circulation and causes an increase in concentrations of both VWF Ag and Factor VIII (FVIII), but has negligible effect on the activity of either. At higher doses, BT200 blocks clearance of VWF and also inhibits its activity, but still does not inhibit FVIII activity. Therefore, low dose BT200 could potentially be used to correct deficiency of VWF and/or FVIII in patients with hereditary bleeding disorders. This study is designed as a "basket design" pilot study to determine the relevant dose and pharmacological activity of BT200 in such patients.
In this open basket study up to 25 patients with the following congenital blood-clotting disorders are to be included: Patients with hemophilia A, heterozygous carriers of hemophilia A with subnormal FVIII levels; patients with von Willebrand syndrome (VWD) type 1, "Vicenza type", and with VWD type 2b.
Participants will receive BT200 subcutaneously on day 0, day 4 and day 7 in the first week and then once a week for a total of five weeks - initially in a dose of 3 mg, then in week 3 individually after response in a dose of 3 to 9 mg.
Subsequently, blood samples are taken once a week for a further three weeks (wash-out phase).
Patients may be enrolled in an additional pharmacokinetics sub-study. For this purpose, approximately three blood samples are taken to estimate the half-life of substituted FVIII under the influence of BT200.
The primary objective of this study is to obtain clinical proof of mechanism for BT200 in one or more hereditary bleeding disorders.

Start Date14 Dec 2020

Sponsor / Collaborator

Medical University of Vienna

100 Clinical Results associated with Rondaptivon Pegol

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100 Translational Medicine associated with Rondaptivon Pegol

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100 Patents (Medical) associated with Rondaptivon Pegol

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13

Literatures (Medical) associated with Rondaptivon Pegol

01 Jan 2025·Journal of Thrombosis and Haemostasis

Aptamer BT200 is protective against myocardial ischemia-reperfusion injury in mice

Article

Author: Yuan, Ancai ; Liao, Xianying ; Ma, Yue ; Chen, Xinyuan ; Wang, Ruowen ; Xie, Yuquan ; Lu, Guiping ; Pu, Jun

BACKGROUNDMyocardial ischemia-reperfusion (MI/R) injury tends to affect cardiac function and leads to poor patient prognosis, and there is still no effectively targeted drug to develop anti-von Willebrand factor (VWF) aptamer in acute coronary heart disease. However, the newly anti-VWF aptamer BT200 is applied not only for stroke and hemophilia but also for antithrombolism function in clinical development. The role of BT200 in acute myocardial injury during MI/R is still unknown.OBJECTIVESTo investigate the cardioprotective effect of aptamer BT200 in a mouse model of MI/R.METHODSC57BL/6 mice were subjected to 30-minute ischemia and 24-hour reperfusion to establish MI/R model. Mice were treated with intravenous injection of cy3-labeled BT200 and were observed by an in vivo imaging system at different time points. Then, mice were sampled and evaluated by echocardiography, Evans triphenyltetrazolium chloride staining, histopathologic, western blotting, and real-time quantitative polymerase chain reaction assays to detect cardiac injury and inflammation response after 24-hour reperfusion.RESULTSBT200 aptamer can enter and infiltrate into the ischemic myocardium after 24-hour reperfusion. BT200 was shown to inhibit VWF A1 activity and prolong bleeding time in MI/R mice. Moreover, BT200-treated mice had a significant reduction in infarct size and an improvement in cardiac function post-MI/R. BT200 treatment can also alleviate MI/R-induced microvascular obstruction, inflammation response, and cardiomyocyte apoptosis.CONCLUSIONPharmacologic targeting of VWF with BT200 alleviates acute MI/R injury in a murine model and may be a novel therapy strategy for acute myocardial infarction.

26 Sep 2024·Blood

The aptamer BT200 blocks interaction of K1405-K1408 in the VWF-A1 domain with macrophage LRP1

Article

Author: Baker, Ross I. ; Gilbert, James C. ; Lopes, Patricia ; Byrne, Ciara ; Amin, Aamir ; Atiq, Ferdows ; Zhu, Shuhao ; Chion, Alain ; Fazavana, Judicael ; Preston, Roger J. S. ; O’Donnell, James S. ; Karampini, Ellie ; Jilma, Bernd ; Aguila, Sonia ; Doherty, Dearbhla ; McKinnon, Thomas A. J. ; Emsley, Jonas

AbstractRondaptivon pegol (previously BT200) is a pegylated RNA aptamer that binds to the A1 domain of von Willebrand factor (VWF). Recent clinical trials demonstrated that BT200 significantly increased plasma VWF–factor VIII levels by attenuating VWF clearance. The biological mechanism(s) through which BT200 attenuates in vivo clearance of VWF has not been defined. We hypothesized that BT200 interaction with the VWF-A1 domain may increase plasma VWF levels by attenuating macrophage-mediated clearance. We observed that full-length and VWF-A1A2A3 binding to macrophages and VWF-A1 domain binding to lipoprotein receptor–related protein 1 (LRP1) cluster II and cluster IV were concentration-dependently inhibited by BT200. Additionally, full-length VWF binding to LRP1 expressed on HEK293T (HEK-LRP1) cells was also inhibited by BT200. Importantly, BT200 interacts with the VWF-A1 domain in proximity to a conserved cluster of 4 lysine residues (K1405, K1406, K1407, and K1408). Alanine mutagenesis of this K1405-K1408 cluster (VWF-4A) significantly (P < .001) attenuated binding of VWF to both LRP1 clusters II and IV. Furthermore, in vivo clearance of VWF-4A was significantly (P < .001) reduced than that of wild-type VWF. BT200 did not significantly inhibit binding of VWF-4A to LRP1 cluster IV or HEK-LRP1 cells. Finally, BT200 interaction with the VWF-A1 domain also inhibited binding to macrophage galactose lectin and the SR-AI scavenger receptor. Collectively, our findings demonstrate that BT200 prolongs VWF half-life by attenuating macrophage-mediated clearance and specifically the interaction of K1405-K1408 in the VWF-A1 domain with macrophage LRP1. These data support the concept that targeted inhibition of VWF clearance pathways represents a novel therapeutic approach for von Willebrand disease and hemophilia A.

23 Jul 2024·Expert Opinion on Pharmacotherapy

Factor VIII stimulants and other novel therapies for the treatment of von Willebrand disease: what’s new on the horizon?

Review

Author: Sidonio, Robert F. ; Regling, Katherine

INTRODUCTIONVon Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting about 0.6% to 1.3% of the population, and is characterized primarily by mucocutaneous bleeding secondary to defective platelet adhesion and aggregation. Current therapeutic options for those with severe disease are limited and require frequent intravenous infusions.AREAS COVEREDThis review discusses the current and recently completed clinical trials involving pathways to FVIII augmentation for the treatment of VWD. Clinical trials registered on clinicaltrials.gov and published data via PubMed searches through June 2024 were included.EXPERT OPINIONAvailable treatment options to those with VWD are limited in part due to limited clinical trials, the complexity of VWD types, and the pharmacokinetics of current treatment options. The development of therapeutic options that reduce treatment burden is necessary to improve quality of life and reduce bleeding complications and in recent years there has been an increased interest from industry to apply novel therapeutics for VWD. The FVIII mimetic, emicizumab, has demonstrated early success in patients with severe VWD and is a promising treatment option for those who require prophylaxis. Furthermore, products like efanesoctocog alfa (Altuviiio®) and BT200 have achieved enhanced VWF/FVIII half-life extension could expand the current treatment landscape while concurrently minimizing treatment burden.

100 Deals associated with Rondaptivon Pegol

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemophilia A	Phase 3	United States	Band Therapeutics LLC	30 Jan 2022
Von Willebrand Disease, Type 2	Phase 3	United States	Band Therapeutics LLC	30 Jan 2022
Von Willebrand Disease, Type 1	Phase 2	United States	Band Therapeutics LLC	30 Jan 2022
Von Willebrand Disease, Type 3	Phase 2	United States	Band Therapeutics LLC	30 Jan 2022
Atherosclerosis	Discovery	Austria	Band Therapeutics LLC	07 Oct 2019
Intracranial Arteriosclerosis	Discovery	Austria	Band Therapeutics LLC	07 Oct 2019
Stroke	Discovery	Austria	Band Therapeutics LLC	07 Oct 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISTH2021	Phase 2	Hemophilia A	-	BT200	iuzusiqzyt(qbvbbojvcn) = iifqmteigg wdeirqatnd (ivktxmqevp, 129 - 421) View more	-	17 Jul 2021
ISTH2021	Phase 2	Von Willebrand Disease, Type 2	5	BT200	vyoaswsoso(blooarlafq) = ejzpydpgaf dufyrptift (fqbpxmznhx ) View more	-	17 Jul 2021