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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Pharmacokinetics of Plasminogen, Human-tvmh in Subjects with Plasminogen Deficiency Type 1 Karen Thibaudeau1, Joseph Parker2, Pierre Chelle3, Andrea Edginton3, Amy Shapiro4, . 1Kedrion Biopharma Inc, Laval, QC, Canada.2Kedrion Biopharma Inc, Fort Lee, NJ, USA.3University of Waterloo, Waterloo, ON, Canada.4Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA |
Abstract
Background: Plasminogen deficiency type 1 (PLGD-1) or hypoplasminogenemia is an ultra-rare disease characterized by a reduction of both plasminogen activity and antigen levels, resulting in accumulation of extra-vascular fibrin-rich lesions on mucosal surfaces. Plasminogen, human-tvmh (PLG) is a plasma derived human plasminogen concentrate indicated for the treatment of subjects with PLGD-1 and FDA-approved in 2021 in the US. It is a lyophilized formulation containing the native circulating form of plasminogen, Glu-plasminogen, reported to have a longer t1/2 (2.2 days) than Lys‑plasminogen (0.8 days) in healthy subjects. Objectives: The (PK) characteristics of PLG administered IV to adults and children with PLGD-1 were assessed in phase 1 and phase 2/3 studies. Dosing intervals were determined based on individual PK profiles with the aim to increase and maintain plasminogen activity trough levels by at least an absolute 10% above baseline. Here are reported the PK properties of single and repeated doses of PLG administered every 2 to 4 days for 12 weeks in subjects with PLGD-1. Methods: A total of 15 subjects (9 adult and 6 pediatric subjects; 4 males and 11 females, 4 to 42 years of age) were administered 6.6 mg/kg PLG every 2 to 4 days for at least 48 weeks. Both plasminogen activity and antigen levels were measured using validated methods and baseline-adjusted PK parameters were derived from concentration-time curves using non-compartmental analysis (NCA). Results: All subjects were included in the PK population and received an actual dose of 5.6-6.8 mg/kg PLG infused over 10 to 17 minutes. Plasminogen activity Similar plasminogen activity profiles were observed in the adult and pediatric PK populations. Mean (± standard deviation [SD]) absolute plasminogen activity was 22.1 ± 12.9% before the first dose and reached a trough level of 51.0 ± 12.0% after 12 weeks of treatment. Mean (± SD) PLG peak concentration (Cmax) increased from 95 ± 23.5% after the first dose to 125 ± 23.3% after 12 weeks of treatment. Mean (± SD) PLG terminal half-life (t1/2) was 34.0 ± 11.7 hours after the first dose and increased slightly to 39.2 ± 6.2 hours after 12 weeks. Individual plasminogen activity trough levels were successfully increased and maintained by at least an absolute 10% above baseline. Plasminogen antigen Similar plasminogen antigen profiles were observed in the adult and pediatric PK populations. However, larger variability was observed in plasminogen antigen levels compared to plasminogen activity, which did not allow reliable interpretation of plasminogen antigen levels and associated PK parameters. Conclusion: PLG administered IV at a dose of 6.6 mg/kg every 2 to 4 days increased plasminogen activity to physiological levels with no safety concerns. Dosing interval based on each individual PK profile obtained after the first dose adequately maintained plasminogen activity trough levels by at least 10% above baseline during 12 weeks of treatment. Robust plasminogen activity data obtained during phase 1 and phase 2/3 studies were used for the development of a population PK model supporting prophylactic replacement therapy for PLGD-1 patients that was successfully integrated into the WAPPS-Hemo platform.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.