Rondaptivon Pegol (BT200) to Correct Thrombocytopenia in a Peri-Interventional Setting in Type 2B Von Willebrand Disease (VWD)

Introduction

Type 2B von Willebrand disease (VWD) is a qualitative VWF defect with increased binding of VWF to platelets, increased platelet clearance, potential thrombocytopenia and a substantial risk of bleeding. Rondaptivon pegol (BT200) is an aptamer binding to the A1 domain of von Willebrand Factor (VWF), which increases VWF antigen, GpIbM, collagen binding activity, multimers and platelet counts in type 2B VWD.

Methods, intervention and outcome

Two thrombocytopenic patients with type 2B VWD received BT200 peri-interventionally. Patient #1 had a suspect lesion in the lung and required bronchoscopy. As she had received BT200 in a previous phase 2 trial, she now received a loading dose of 10 mg BT200 prior to the procedure, which increased platelet counts from 46 to 108 x10E9/L after one week. Subsequent doses of BT200 normalized her platelet counts. Two months later, she received a loading dose of 12mg, 7.5 and 7.5mg BT200 at weekly intervals before an enteroscopy with thermocoagulation because of frequent bleedings due to jejunal angiodysplasia. Her platelet counts reached 160 before and 153 x10E9/L after the intervention. In both cases BT200 made it possible to conduct those diagnostic procedures, for which threshold platelet counts above the patient's baseline are required. No bleeding complications occurred.

The second patient had a femoral neck fracture that required hip surgery under prophylactic substitution wirh Haemate P, which increased VWF activity to 101%. Nevertheless, platelet counts continued to fall to 14 x10E9/L, and the patient not only showed extensive local hematomas, but also developed bleedings at distant sites (buccal, extremities). This strongly indicates that those bleedings resulted from severe thrombocytopenia, because VWF activity was normal under substitution therapy. BT200 (4.5mg) was injected four days after surgery which increased platelet counts from 25 to 49 x10E9/L after one week. A second dose of 7.5 mg increased platelet counts to 278 x10E9/L after another week.

Conclusion

BT200 corrected platelet counts facilitating two successful interventions without bleeding complications in one patient and a cessation of bleeding in a second patient, which indicates the utility of BT200 in the peri-interventional setting.

Literature

Ay C, et al. The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease. Blood Advances. 2022;27;6(18):5467-5476.

Cihon A, et al. Aptamer BT200 blocks interaction of K1405-1408 in the VWF-A1 domain with macrophage LRP1. Blood. 2024 Jul 12:blood.2024024055

Ay:BMS, Pfizer, Daiichi-Sankyo, Bayer, Sanofi, Novo Nordisk, CSL Behring, Sobi, Roche: Honoraria, Speakers Bureau. Schoergenhofer:Vega Therapeutics, Inc.: Honoraria, Research Funding. Gilbert:Band Therapeutics LLC a Guardian Therapeutics company: Current Employment, Current equity holder in private company. Zhu:Band Therapeutics LLC, a Guardian Therapeutics company.: Current Employment, Current equity holder in private company. Jilma:Band Therapeutics, LLC: Consultancy.