Kinetic Modeling for BT200 to Predict the Level of Plasma-Derived Coagulation Factor VIII in Humans.
BT200
factor VIII
pharmacokinetic and pharmacodynamic modeling
population pharmacokinetic modeling
rondaptivon pegol
Journal
The AAPS journal
ISSN: 1550-7416
Titre abrégé: AAPS J
Pays: United States
ID NLM: 101223209
Informations de publication
Date de publication:
12 Jul 2024
12 Jul 2024
Historique:
received:
07
05
2024
accepted:
19
06
2024
medline:
12
7
2024
pubmed:
12
7
2024
entrez:
11
7
2024
Statut:
epublish
Résumé
Lack of Factor VIII (FVIII) concentrates is one of limiting factors for Hemophilia A prophylaxis in resource-limited countries. Rondaptivon pegol (BT200) is a pegylated aptamer and has been shown to elevate the level of von Willebrand Factor (VWF) and FVIII in previous studies. A population pharmacokinetic model for BT200 was built and linked to the kinetic models of VWF and FVIII based on reasonable assumptions. The developed PK/PD model for BT200 described the observed kinetic of BT200, VWF, and FVIII in healthy volunteers and patients with mild-to-moderate hemophilia A from two clinical trials. The developed model was evaluated using an external dataset in patients with severe hemophilia A taking recombinant FVIII products. The developed and evaluated PK/PD model was able to describe and predict concentration-time profiles of BT200, VWF, and FVIII in healthy volunteers and patients with hemophilia A. Concentration-time profiles of FVIII were then predicted following coadministration of plasma-derived FVIII concentrate and BT200 under various dosing scenarios in virtual patients with severe hemophilia A. Plasma-derived products, that contain VWF, are more accessible in low-resource countries as compared to their recombinant counterparts. The predicted time above 1 and 3 IU/dL FVIII in one week was compared between scenarios in the absence and presence of BT200. A combination dose of 6 mg BT200 once weekly plus 10 IU/kg plasma-derived FVIII twice weekly maintained similar coverage to a 30 IU/kg FVIII thrice weekly dose in absence of BT200, representing only 22% of the FVIII dose per week.
Identifiants
pubmed: 38992298
doi: 10.1208/s12248-024-00952-4
pii: 10.1208/s12248-024-00952-4
doi:
Substances chimiques
Factor VIII
9001-27-8
von Willebrand Factor
0
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
81Informations de copyright
© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
Références
Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(S6):1–158.
Ndoumba-Mintya A, Diallo YL, Tayou TC, Mbanya DN. Optimizing Haemophilia Care in Resource-Limited Countries: Current Challenges and Future Prospects. J Blood Med. 2023;14:141–6.
doi: 10.2147/JBM.S291536
pubmed: 36846349
pmcid: 9951595
Sidharthan N, Sudevan R. Low Dose Prophylaxis in Hemophilia Care. Indian J Hematol Blood Trans. 2020;36(1):16–25.
doi: 10.1007/s12288-019-01147-0
Kwak H, Lee S, Jo S, Kwon YE, Kang H, Choi G, et al. MG1113, a specific anti–tissue factor pathway inhibitor antibody, rebalances the coagulation system and promotes hemostasis in hemophilia. Res Pract Thromb Haemost. 2020;4(8):1301–12.
doi: 10.1002/rth2.12438
pubmed: 33313469
pmcid: 7695563
Malec L, Matino D. Targeting higher factor VIII levels for prophylaxis in haemophilia A: a narrative review. Haemophilia. 2023;29(6):1419–29.
doi: 10.1111/hae.14866
pubmed: 37758651
Seth T, Garg K, Mandal PK, Datta A, Verma S, Hanagavadi S, et al. Cost-effectiveness analysis of low-dose prophylaxis versus on-demand treatment for moderate-to-severe hemophilia A in India. Hematology. 2023;28(1):2277497.
doi: 10.1080/16078454.2023.2277497
pubmed: 37933875
Brekkan A, Degerman J, Jönsson S. Model-based evaluation of low-dose factor VIII prophylaxis in haemophilia A. Haemophilia. 2019;25(3):408–15.
doi: 10.1111/hae.13753
pubmed: 31050134
Ay C, Kovacevic KD, Kraemmer D, Schoergenhofer C, Gelbenegger G, Firbas C, et al. The von Willebrand Factor-Binding Aptamer Rondaptivon Pegol as a Treatment for Severe and Nonsevere Hemophilia A. Blood. 2023;141(10):1147–58.
doi: 10.1182/blood.2022016571
pubmed: 36108308
Kovacevic KD, Buchtele N, Schoergenhofer C, Derhaschnig U, Gelbenegger G, Brostjan C, et al. The Aptamer BT200 Effectively Inhibits von Willebrand Factor (VWF) Dependent Platelet Function After Stimulated VWF Release by Desmopressin or Endotoxin. Sci Rep. 2020;10(1):11180.
doi: 10.1038/s41598-020-68125-9
pubmed: 32636459
pmcid: 7341806
Kovacevic KD, Grafeneder J, Schörgenhofer C, Gelbenegger G, Gager G, Firbas C, et al. The von Willebrand Factor A-1 Domain Binding Aptamer BT200 Elevates Plasma Levels of von Willebrand Factor and Factor VIII: A First-In-Human Trial. Haematologica. 2022;107(9):2121–32.
doi: 10.3324/haematol.2021.279948
pubmed: 34818873
Zhu S, Gilbert JC, Liang Z, Kang D, Li M, Tarantino PM, et al. Potent and Rapid Reversal of the von Willebrand Factor Inhibitor Aptamer BT200. J Thromb Haemost. 2020;18(7):1695–704.
doi: 10.1111/jth.14822
pubmed: 32275107
pmcid: 7384040
Turecek PL, Johnsen JM, Pipe SW, O’Donnell JS. the i Psg. Biological Mechanisms Underlying Inter-Individual Variation in Factor VIII Clearance in Haemophilia. Haemophilia. 2020;26(4):575–83.
doi: 10.1111/hae.14078
pubmed: 32596930
pmcid: 7496649
Choin A, Aguila S, Fazavana J, Byrne C, Ward S, O’Sullivan J, et al., editors. Aptamer BT200 prolongs VWF half-life by blocking interaction with macrophage scavenger receptor LRP1. International Society on Thrombosis and Haemostasis; 2023; Montréal, Canada.
Grifols Biologicals Inc. Package Insert - Alphanate2018. Available from: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/alphanate . Accessed 21 Apr 2023.
Honda S, Shimahara Y, Chikasawa Y, Ogino H. Hemostatic protocol and risk-reduction surgery for treating coronary artery disease with aortic stenosis in a patient with combined coagulation factor VIII and XI deficiency: a case report. Eur Heart J Case Rep. 2023;7(5):ytad219.
doi: 10.1093/ehjcr/ytad219
pubmed: 37168362
pmcid: 10166512
Beal SL, Sheiner LB, Boeckman AJ, Bauer RJ. NONMEM 7.4 Users Guide1989–2018. Available from: https://nonmem.iconplc.com/nonmem743/guides . Accessed 22 May 2023.
Bauer RJ. NONMEM Tutorial Part I: Description of Commands and Options, With Simple Examples of Population Analysis. CPT Pharmacometrics Syst Pharmacol. 2019;8(8):525–37.
doi: 10.1002/psp4.12404
pubmed: 31056834
pmcid: 6709426
R Core Team. R: A Language and Environment for Statistical Computing2023. Available from: https://www.R-project.org/ . Accessed 20 Mar 2023.
Beal SL. Ways to Fit a PK Model with Some Data Below the Quantification Limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481–504.
doi: 10.1023/A:1012299115260
pubmed: 11768292
McEneny-King A, Chelle P, Foster G, Keepanasseril A, Iorio A, Edginton AN. Development and Evaluation of a Generic Population Pharmacokinetic Model for Standard Half-Life Factor VIII for Use in Dose Individualization. J Pharmacokinet Pharmacodyn. 2019;46(5):411–26.
doi: 10.1007/s10928-019-09634-7
pubmed: 31104228
Bukkems LH, Heijdra JM, de Jager NCB, Hazendonk HCAM, Fijnvandraat K, Meijer K, et al. Population pharmacokinetics of the von Willebrand factor-factor VIII interaction in patients with von Willebrand disease. Blood Adv. 2021;5(5):1513–22.
doi: 10.1182/bloodadvances.2020003891
pubmed: 33683340
pmcid: 7948283
Ng C, Motto DG, Di Paola J. Diagnostic approach to von Willebrand disease. Blood. 2015;125(13):2029–37.
doi: 10.1182/blood-2014-08-528398
pubmed: 25712990
pmcid: 4375103
Chelle P, Yeung CHT, Croteau SE, Lissick J, Balasa V, Ashburner C, et al. Development and Validation of a Population-Pharmacokinetic Model for Rurioctacog Alfa Pegol (Adynovate®): A Report on Behalf of the WAPPS-Hemo Investigators Ad Hoc Subgroup. Clin Pharmacokinet. 2020;59(2):245–56.
doi: 10.1007/s40262-019-00809-6
pubmed: 31435896
Dayneka NL, Garg V, Jusko WJ. Comparison of Four Basic Models of Indirect Pharmacodynamic Responses. J Pharmacokinet Biopharm. 1993;21(4):457–78.
doi: 10.1007/BF01061691
pubmed: 8133465
pmcid: 4207304
Lee M, Jeong Y-S, Kim M-S, An K-M, Chung S-J. Prediction of Pharmacokinetics of IDP-73152 in Humans Using Physiologically-Based Pharmacokinetics. Pharmaceutics [Internet]. 2022; 14(6).
Keating GM, Dhillon S. Octocog Alfa (Advate®): A Guide to Its Use in Hemophilia A. BioDrugs. 2012;26(4):269–73.
doi: 10.1007/BF03261885
pubmed: 22759264
Yamaoka K, Nakagawa T, Uno T. Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm. 1978;6(6):547–58.
doi: 10.1007/BF01062109
pubmed: 731417
Lee W, Kim M-S, Kim J, Aoki Y, Sugiyama Y. Predicting In Vivo Target Occupancy (TO) Profiles via Physiologically Based Pharmacokinetic–TO Modeling of Warfarin Pharmacokinetics in Blood: Importance of Low Dose Data and Prediction of Stereoselective Target Interactions. Drug Metab Dispos. 2023;51(9):1145.
doi: 10.1124/dmd.122.000968
pubmed: 36914276
West GB, Brown JH, Enquist BJ. A General Model for the Origin of Allometric Scaling Laws in Biology. Science. 1997;276(5309):122–6.
doi: 10.1126/science.276.5309.122
pubmed: 9082983
McLeay SC, Morrish GA, Kirkpatrick CMJ, Green B. The Relationship between Drug Clearance and Body Size. Clin Pharmacokinet. 2012;51(5):319–30.
doi: 10.2165/11598930-000000000-00000
pubmed: 22439649
Chelle P, Yeung CHT, Bonanad S, Morales Muñoz JC, Ozelo MC, MegíasVericat JE, et al. Routine Clinical Care Data for Population Pharmacokinetic Modeling: The Case for Fanhdi/Alphanate in Hemophilia a Patients. J Pharmacokinet Pharmacodyn. 2019;46(5):427–38.
doi: 10.1007/s10928-019-09637-4
pubmed: 31115857
pmcid: 6820598
Al-Sallami HS, Goulding A, Grant A, Taylor R, Holford N, Duffull SB. Prediction of Fat-Free Mass in Children. Clin Pharmacokinet. 2015;54(11):1169–78.
doi: 10.1007/s40262-015-0277-z
pubmed: 25940825
Sinha J, Duffull SB, Al-Sallami HS. A Review of the Methods and Associated Mathematical Models Used in the Measurement of Fat-Free Mass. Clin Pharmacokinet. 2018;57(7):781–95.
doi: 10.1007/s40262-017-0622-5
pubmed: 29330781
Michaela M, Sebastian S, Bernd L, Lars K, Joerg L. Using Expression Data for Quantification of Active Processes in Physiologically Based Pharmacokinetic Modeling. Drug Metab Dispos. 2012;40(5):892.
doi: 10.1124/dmd.111.043174
Jiménez-Yuste V, Auerswald G, Benson G, Lambert T, Morfini M, Remor E, et al. Achieving and maintaining an optimal trough level for prophylaxis in haemophilia: the past, the present and the future. Blood Transfus. 2014;12(3):314–9.
pubmed: 25074524
pmcid: 4111811
Collins PW, Blanchette VS, Fischer K, Björkman S, Oh M, Fritsch S, et al. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost. 2009;7(3):413–20.
doi: 10.1111/j.1538-7836.2008.03270.x
pubmed: 19143924
Den Uijl IEM, Mauser Bunschoten EP, Roosendaal G, Schutgens REG, Biesma DH, Grobbee DE, et al. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011;17(6):849–53.
doi: 10.1111/j.1365-2516.2011.02539.x
Machin N, Ragni MV, Smith KJ. Gene therapy in hemophilia A: a cost-effectiveness analysis. Blood Adv. 2018;2(14):1792–8.
doi: 10.1182/bloodadvances.2018021345
pubmed: 30042145
pmcid: 6058236
Srinivasan M, White A, Chaturvedula A, Vozmediano V, Schmidt S, Plouffe L, et al. Incorporating Pharmacometrics into Pharmacoeconomic Models: Applications from Drug Development. Pharmacoeconomics. 2020;38(10):1031–42.
doi: 10.1007/s40273-020-00944-0
pubmed: 32734572
pmcid: 7578131
Hill-McManus D, Marshall S, Liu J, Willke RJ, Hughes DA. Linked Pharmacometric-Pharmacoeconomic Modeling and Simulation in Clinical Drug Development. Clin Pharmacol Ther. 2021;110(1):49–63.
doi: 10.1002/cpt.2051
pubmed: 32936931
Richter A, Anton SE, Koch P, Dennett SL. The impact of reducing dose frequency on health outcomes. Clin Ther. 2003;25(8):2307–35.
doi: 10.1016/S0149-2918(03)80222-9
pubmed: 14512137
Evans M, Jensen HH, Bøgelund M, Gundgaard J, Chubb B, Khunti K. Flexible insulin dosing improves health-related quality-of-life (HRQoL): a time trade-off survey. J Med Econ. 2013;16(11):1357–65.
doi: 10.3111/13696998.2013.846262
pubmed: 24111563
Grossman HA, Goon B, Bowers P, Leitz G, Study G. Once-Weekly Epoetin Alfa Dosing Is as Effective as Three Times–Weekly Dosing in Increasing Hemoglobin Levels and Is Associated With Improved Quality of Life in Anemic HIV-Infected Patients. J Acquir Immune Defic Syndr. 2003;34(4).
Reginster JY, Rabenda V, Neuprez A. Adherence, patient preference and dosing frequency: Understanding the relationship. Bone. 2006;38(4, Supplement 1):S2–6.
doi: 10.1016/j.bone.2006.01.150
pubmed: 16520104
Kamphuisen PW, Eikenboom JCJ, Bertina RM. Elevated Factor VIII Levels and the Risk of Thrombosis. Arterioscler Thromb Vasc Biol. 2001;21(5):731–8.
doi: 10.1161/01.ATV.21.5.731
pubmed: 11348867