Factor IX stimulants in preclinical and early phase trials for hemophilia B treatment

REFERENCES

• Franchini M, Mannucci PM. Past, present and future of hemophilia: a narrative review. Orphanet J Rare Dis. 2012;7(1):24. doi: 10.1186/1750-1172-7-24
   PubMed Web of Science ®Google Scholar
• Bolton-Maggs PH, Pasi KJ. Haemophilia A and B. Lancet. 2003;361(9371):1801–9. doi: 10.1016/S0140-6736(03)13405-8
   PubMed Web of Science ®Google Scholar
• Mannucci PM, Tuddenham EG. The hemophilias – from royal genes to gene therapy. N Engl J Med. 2001;344(23):1773–9. doi: 10.1056/NEJM200106073442307
   PubMed Web of Science ®Google Scholar
• Tagariello G, Belvini D, Salviato R, et al. The Italian haemophilia B pathogenic variant database: a tool for genetic counselling, carrier detection and prenatal diagnosis. Blood Transfus. 2007;5(3):158–63. doi: 10.2450/2007.0024-07
   PubMedGoogle Scholar
• Perez Botero J, Coon LM, Majerus JA, et al. Factor IX Gene (F9) Genotyping Trends and Spectrum of Pathogenic variants Identified: A Reference Laboratory Experience. Semin Thromb Hemost. 2018;44(3):287–92. doi: 10.1055/s-0037-1605567
   PubMed Web of Science ®Google Scholar
• Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. The Lancet. 2016;388(10040):187–197. doi: 10.1016/S0140-6736(15)01123-X
   PubMed Web of Science ®Google Scholar
• Tagariello G, Iorio A, Santagostino E, et al.; Italian Association Hemophilia Centre (AICE). Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders. Blood. 2009;114(4):779–784. doi: 10.1182/blood-2009-01-195313
   PubMed Web of Science ®Google Scholar
• Franchini M, Mannucci PM. Haemophilia B is clinically less severe than haemophilia A: further evidence. Blood Transfus. 2018;16(2):121–122. doi: 10.2450/2016.0158-16
   PubMed Web of Science ®Google Scholar
• Mannucci PM, Franchini M. Is haemophilia B less severe than haemophilia A? Haemophilia. 2013;19(4):499–502. doi: 10.1111/hae.12133
   PubMed Web of Science ®Google Scholar
• Clausen N, Petrini P, Claeyssens-Donadel S, et al.; PedNet and Research of Determinants of Inhibitor development (RODIN) Study Group. Similar bleeding phenotype in young children with haemophilia A or B: a cohort study. Haemophilia. 2014;20(6):747–755. doi: 10.1111/hae.12470.
   PubMed Web of Science ®Google Scholar
• Franchini M, Zaffanello M, Focosi D Current factor IX replacement options for hemophilia B and the challenges ahead. Expert Opin Pharmacother. 2023;24(6):729–736. doi: 10.1080/14656566.2023.2196012 ∙∙ An updated overview of current replacement therapies for hemophilia B.
   PubMed Web of Science ®Google Scholar
• Franchini M. Current management of hemophilia B: recommendations, complications and emerging issues. Expert Rev Hematol. 2014;7(5):573–81. doi: 10.1586/17474086.2014.947955
   PubMed Web of Science ®Google Scholar
• Mannucci PM, Franchini M. Emerging drugs for hemophilia B. Expert Opin Emerg Drugs. 2014;19(3):407–414. doi: 10.1517/14728214.2014.946010
   PubMed Web of Science ®Google Scholar
• Franchini M, Frattini F, Crestani S, et al. Haemophilia B: current pharmacotherapy and future directions. Expert Opin Pharmacother. 2012;13(14):2053–2063. doi: 10.1517/14656566.2012.721780
   PubMed Web of Science ®Google Scholar
• Srivastava A, Santagostino E, Dougall A, et al.; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26 Suppl 6:1–158. doi: 10.1111/hae.14046 ∙∙ Evidence-based recommendations on the management of hemophilia.
   PubMed Web of Science ®Google Scholar
• Thachil J, Connors JM, Mahlangu J, et al. Reclassifying hemophilia to include the definition of outcomes and phenotype as new targets. J Thromb Haemost. 2023;21(7):1737–1740. doi: 10.1016/j.jtha.2023.03.016
   PubMed Web of Science ®Google Scholar
• Fassel H, McGuinn C. Haemophilia: factoring in new therapies. Br J Haematol. 2021;194(5):835–850. doi: 10.1111/bjh.17580
   PubMed Web of Science ®Google Scholar
• Marchesini E, Morfini M, Valentino L Recent Advances in the Treatment of Hemophilia: A Review. Biologics. 2021:15:221–235. doi: 10.2147/BTT.S252580
   PubMed Web of Science ®Google Scholar
• Mancuso ME, Mahlangu JN, Pipe SW. The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing. The Lancet. 2021;397(10274):630–640. doi: 10.1016/S0140-6736(20)32722-7
   PubMed Web of Science ®Google Scholar
• Lillicrap D. Evaluating the potential benefits of the extravascular pool of factor IX. Blood Coagul Fibrinolysis. 2021;32(1):68–69. doi: 10.1097/MBC.0000000000000969
   PubMed Web of Science ®Google Scholar
• Peyvandi F, Garagiola I, Seregni S. Future of coagulation factor replacement therapy. J Thromb Haemost. 2013;11 Suppl 1:84–98. doi: 10.1111/jth.12270
   PubMed Web of Science ®Google Scholar
• Weyand AC, Pipe SW. New therapies for hemophilia. Blood. 2019;133(5):389–398. doi: 10.1182/blood-2018-08-872291
   PubMed Web of Science ®Google Scholar
• Lamb YN, Hoy, SM. Eftrenonacog Alfa: A Review in Haemophilia B. Drugs. 2023;83(9):807–18. doi: 10.1007/s40265-023-01868-7
   PubMed Web of Science ®Google Scholar
• Powell JS, Pasi KJ, Ragni MV, et al.; B-LONG Investigators. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013;369(24):2313–2323. doi: 10.1056/NEJMoa1305074
   PubMed Web of Science ®Google Scholar
• Fischer K, Kulkarni R, Nolan B, et al. Recombinant factor IX fc fusion protein in children with haemophilia B (kids B-LONG): results from a multicentre, non-randomised phase 3 study. Lancet Haematol. 2017;4(2):e75–e82. doi: 10.1016/S2352-3026(16)30193-4
   PubMed Web of Science ®Google Scholar
• Nolan B, Klukowska A, Shapiro A, et al. Final results of the PUPs B-LONG study: evaluating safety and efficacy of rFIXFc in previously untreated patients with hemophilia B. Blood Adv. 2021 Jul 13;5(13):2732–2739. doi: 10.1182/bloodadvances.2020004085.
   PubMed Web of Science ®Google Scholar
• Pasi KJ, Fischer K, Ragni M, et al. Long-term safety and sustained efcacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: results from the B-YOND extension study. Haemophilia. 2020;26(6):e262–71.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. ALPROLIX (eftrenonacog alfa): EU public assessment report; 2016. http://www.ema.europa.eu/. Accessed 22 February 2024.
   Google Scholar
• Østergaard H, Bjelke JR, Hansen L, et al. Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide. Blood. 2011;118(8):2333–2341. doi: 10.1182/blood-2011-02-336172.
   PubMed Web of Science ®Google Scholar
• Negrier C, Knobe K, Tiede A, et al. Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011;118(10):2695–2701. doi: 10.1182/blood-2011-02-335596.
   PubMed Web of Science ®Google Scholar
• Collins PW, Møss J, Knobe K, et al. Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. J Thromb Haemost. 2012;10(11):2305–2312. doi: 10.1111/jth.12000. PMID: 22998153.
   PubMed Web of Science ®Google Scholar
• Collins PW, Young G, Knobe K, et al. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood. 2014;124(26):3880–3886. doi: 10.1182/blood-2014-05-573055.
   PubMed Web of Science ®Google Scholar
• Escobar MA, Tehranchi R, Karim FA, et al. Low-factor consumption for major surgery in haemophilia B with long-acting recombinant glycoPEGylated factor IX. Haemophilia. 2017 Jan;23(1):67–76. doi: 10.1111/hae.13041.
   PubMed Web of Science ®Google Scholar
• Young G, Collins PW, Colberg T, et al. Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm™4). Thromb Res. 2016 May;141:69–76. doi: 10.1016/j.thromres.2016.02.030.
   PubMed Web of Science ®Google Scholar
• Carcao M, Kearney S, Lu MY, et al. Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B. Thromb Haemost. 2020;120(5):737–746. doi: 10.1055/s-0040-1709521.
   PubMed Web of Science ®Google Scholar
• Chan AK, Alamelu J, Barnes C, et al. Nonacog beta pegol (N9-GP) in hemophilia B: first report on safety and efficacy in previously untreated and minimally treated patients. Res Pract Thromb Haemost. 2020;4(7):1101–1103. doi: 10.1002/rth2.12412
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Refixia (Nonacog beta pegol). https://www.ema.europa.eu/en/medicines/human/EPAR/refixia. Accessed 22 February 2024.
   Google Scholar
• Metzner HJ, Weimer T, Kronthaler U, Lang W, Schulte S. Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. Thromb Haemost. 2009;102(4):634–44. doi: 10.1160/TH09-04-0255.
   PubMed Web of Science ®Google Scholar
• Santagostino E, Martinowitz U, Lissitchkov T, et al.; PROLONG-9FP Investigators Study Group. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016;127(14):1761–1769. doi: 10.1182/blood-2015-09-669234.
   PubMed Web of Science ®Google Scholar
• Kenet G, Chambost H, Male C, et al; PROLONG-9FP Investigator Study Group. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost. 2016;116(4):659–68. doi: 10.1160/TH16-03-0179.
   PubMed Web of Science ®Google Scholar
• Mancuso ME, Lubetsky A, Pan-Petesch B, et al. Long-term safety and efficacy of rIX-FP prophylaxis with extended dosing intervals up to 21 days in adults/adolescents with hemophilia B. J Thromb Haemost. 2020;18(5):1065–1074. doi: 10.1111/jth.14778
   PubMed Web of Science ®Google Scholar
• Kenet G, Chambost H, Male C, et al. Long-Term Safety and Efficacy of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Previously Treated Pediatric Patients with Hemophilia B: Results from a Phase 3b Extension Study. Thromb Haemost. 2020;120(4):599–606. doi: 10.1055/s-0040-1705116.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Idelvion. Idelvion | European Medicines Agency (europa.eu) Accessed 22 February 2024.
   Google Scholar
• Zanon E, Pasca S, Simioni P. The sudden and unexpected appearance of inhibitors in a previously treated severe haemophilia B patient after the switch to albutrepenonacog alpha. Haemophilia. 2018;24(5):e372–5. doi: 10.1111/hae.13590
   PubMed Web of Science ®Google Scholar
• Nichols TC, Levy H, Merricks EP, et al. Preclinical evaluation of a next-generation, subcutaneously administered, coagulation factor IX variant, dalcinonacog alfa. PLoS One. 2020;15(10):e0240896. doi: 10.1371/journal.pone.0240896
   PubMed Web of Science ®Google Scholar
• Hong S-B, Levy H, Jung JY, et al. Pharmacokinetics of subcutaneously administered CB 2679d/ISU304 in wild-type and hemophilia B mice. Blood. 2016;128(22):1389. doi: 10.1182/blood.V128.22.1389.1389
   Web of Science ®Google Scholar
• You CW, Hong SB, Kim S, et al. Safety, pharmacokinetics, and pharmacodynamics of a next-generation subcutaneously administered coagulation factor IX variant, dalcinonacog alfa, in previously treated hemophilia B patients. J Thromb Haemost. 2021;19(4):967–975. doi: 10.1111/jth.15259
   PubMed Web of Science ®Google Scholar
• Mahlangu J, Levy H, Lee M, et al. Efficacy and safety of subcutaneous prophylaxis with dalcinonacog alfa in adults with haemophilia B. Haemophilia. 2021;27(4):574–580. doi: 10.1111/hae.14315.
   PubMed Web of Science ®Google Scholar
• Faraj A, Le Moan N, Gorina E, et al. Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients. Adv Ther. 2023;40(9):3739–3750. doi: 10.1007/s12325-023-02570-6.
   PubMed Web of Science ®Google Scholar
• Lewandowska M, Nasr S, Shapiro AD. Therapeutic and technological advancements in haemophilia care: Quantum leaps forward. Haemophilia. 2022;28 Suppl 4:77–92. doi: 10.1111/hae.14531.
   PubMedGoogle Scholar
• Croteau SE, Wang M, Wheeler AP. 2021 clinical trials update: Innovations in hemophilia therapy. Am J Hematol. 2021;96(1):128–44. doi: 10.1002/ajh.26018.
   PubMed Web of Science ®Google Scholar
• Gogia P, Tarantino M, Schramm W, et al. New directions to develop therapies for people with hemophilia. Expert Rev Hematol. 2023;16(6):417–433. doi: 10.1080/17474086.2023.2184341. ∙∙ An updated review on novel therapies for hemophilia.
   PubMed Web of Science ®Google Scholar
• Simioni P, Tormene D, Tognin G, et al. X-linked thrombophilia with a mutant factor IX (factor IX Padua). N Engl J Med. 2009;361(17):1671–1675. doi: 10.1056/NEJMoa0904377.
   PubMed Web of Science ®Google Scholar
• Liu Z, van der Flier A, Ismail A, et al. Evaluation of recombinant FIXfc-xten bleeding efficacy in hemophilia-B mouse models. Blood. 2016;128(22):3757. doi: 10.1182/blood.V128.22.3757.3757
   Web of Science ®Google Scholar
• Van der Flier A, Ismail A, Moore N, et al. The pharmacokinetic profiles of intravenously and subcutaneously administered recombinant factor IX Fc-XTEN in Cynomolgus Monkeys. Res Pract Theromb Haemost 2017;1(Suppl. 1):98.
   Google Scholar
• Lombardi S, Aaen KH, Nilsen J, et al. Fusion of engineered albumin with factor IX Padua extends half-life and improves coagulant activity. Br J Haematol. 2021;194(2):453–462. doi: 10.1111/bjh.17559.
   PubMed Web of Science ®Google Scholar
• Herzog RW, Nichols TC, Su J, et al. Oral tolerance induction in hemophilia B dogs fed with transplastomic lettuce. Mol Ther. 2017;25(2):512–522. doi: 10.1016/j.ymthe.2016.11.009
   PubMed Web of Science ®Google Scholar
• Srinivasan A, Herzog RW, Khan I, et al. Preclinical development of plant-based oral immune modulatory therapy for haemophilia B. Plant Biotechnol J. 2021;19(10):1952–1966. doi: 10.1111/pbi.13608
   PubMed Web of Science ®Google Scholar
• Franchini M, Mannucci PM. The more recent history of hemophilia treatment. Semin Thromb Hemost. 2022;48(8):904–10. doi: 10.1055/s-0042-1756188. .
   PubMedGoogle Scholar
• Castaman G, Coppens M, Pipe SW. Etranacogene dezaparvovec for the treatment of adult patients with severe and moderately severe hemophilia B. Expert Rev Hematol. 2023;16(12):919–932. doi: 10.1080/17474086.2023.2276206
   PubMed Web of Science ®Google Scholar
• Ay C, Frenzel L, Pinachyan K, et al. Gene therapy for haemophilia A and B, from basic principles to clinical implementation: An illustrated review. Haemophilia. 2024;30(1):5–15. doi: 10.1111/hae.14907.
   PubMed Web of Science ®Google Scholar