Sucrose-Formulated Octocog Alfa
- 114 Downloads
Sucrose-formulated octocog alfa (Kogenate® Bayer, Kogenate® FS, Helixate® FS, Helixate® nexgen) is a full-length recombinant human coagulation factor VIII (FVIII) product that is purified and formulated without the addition of human serum albumin and is stabilized with sucrose. The purification process of this formulation includes a solvent/detergent viral inactivation step. Sucrose-formulated octocog alfa is approved in the EU and US for the treatment of bleeding in patients with haemophilia A (congenital FVIII deficiency). Additionally, it is approved in the EU for the prophylaxis of bleeding in patients with haemophilia A and as a continuous infusion treatment in patients undergoing major surgery.
Sucrose-formulated octocog alfa is effective and well tolerated as a FVIII replacement therapy in patients with haemophilia A, including those with severe disease undergoing major surgery. The therapeutic profile of this sucrose-formulated product cannot be compared with that of other octocog alfa or moroctocog alfa products because of a lack of head-to-head comparative studies. Pathogen transmission has not been reported with use of sucrose-formulated octocog alfa. Available data indicate that sucrose-formulated octocog alfa is an appropriate alternative to other recombinant FVIII products for the treatment and prophylaxis of bleeding episodes in adults and children with haemophilia A.
Sucrose-formulated octocog alfa is produced by baby hamster kidney (BHK) cells transfected with the gene for human FVIII; it has the same biological activity as FVIII derived from human plasma.
Following bolus administration of sucrose-formulated octocog alfa ≈50 IU/kg to previously treated adults and children with severe haemophilia A, mean plasma FVIII levels rose rapidly to over 100% of normal before declining in a biphasic manner, with an elimination half-life that ranged from ≈13 to 19 hours in patients aged 12–60 years (≈11 hours in children aged ≈4–18 years). Sucrose-formulated octocog alfa generally demonstrated bioequivalence to its predecessor product (albumin-formulated octocog alfa) in clinical trials. Reported mean residence time values in individual studies following bolus injection of sucrose-formulated octocog alfa were 18.8 and 22.5 hours in patients aged 12–60 years (15.1 hours in children); reported mean FVIII clearance values were 1.5 and 1.9 dL/h (4.1 mL/h/ kg in children).
Several noncomparative clinical trials and postmarketing surveillance studies have demonstrated that sucrose-formulated octocog alfa is effective replacement therapy for the prophylaxis (both regular and preventative) and treatment of bleeding episodes in previously treated, minimally treated and previously untreated patients (both adults and children) with haemophilia A. In clinical trials, 89–94% of the bleeding episodes were controlled with one or two infusions of sucrose-formulated octocog alfa. Of the clinical responses to the infusion of sucrose-formulated octocog alfa for the treatment of a bleeding episode, 81–100% were rated by the patient or their caregiver or physician as good or excellent.
Sucrose-formulated octocog alfa administered via bolus injection and/or continuous infusion was also effective as replacement therapy in patients with severe haemophilia A undergoing minor or major surgical operations. Surgeons rated haemostasis during or after surgery as good or excellent in all cases; blood losses related to the surgeries performed were minimal or within expected (normal) limits.
In clinical trials, bolus administration of sucrose-formulated octocog alfa to patients with haemophilia A was well tolerated, as was bolus injection or continuous infusion of the drug in patients with severe haemophilia A undergoing surgery. Common adverse events that were considered at least remotely or possibly drug-related included injection site reactions and rash (with or without pruritus) in previously treated patients, and anti-FVIII neutralizing antibody (inhibitor) formation in minimally treated or previously untreated patients. Antibody responses to trace (recombinant FVIII, murine and BHK) proteins in sucrose-formulated octocog alfa (analysed by ELISA) were not associated with drug-related allergic/hypersensitivity adverse events. Sucrose-formulated octocog alfa was not associated with viral transmission or seroconversion.
The development of inhibitors has been evaluated in a meta-analysis of 2071 patients with haemophilia A who received sucrose-formulated octocog alfa (preliminary data). The overall incidence of de novo inhibitor formation was 8.2% in previously untreated patients or those with <20 exposure days and <0.2% in patients with >100 exposure days. The incidence of recurrent inhibitor formation was 7.6%.
- 4.Lusher J, Chitlur M. KogenateFS: antihemophilic factor rFVIII-FS. Therapy 2006; 3(6): 699–708Google Scholar
- 7.Antihemophilic factor (recombinant) Kogenate® FS formulated with sucrose prescribing information. Tarrytown (NY): Bayer Healthcare LLC, 2007 JunGoogle Scholar
- 11.Prescribing information, Wyeth Pharmaceuticals Inc., Philadelphia (PA). XYNTHA® [antihemophilic factor (recombinant), plasma/albumin-free] for intravenous use, freeze-dried powder [online]. Available from URL: http://www.fda.gov/CBER/labeVxyntha022108LB.pdf [Accessed 2008 Mar 11]
- 12.Baxter Healthcare Corporation, Westlake Village (CA). AD-VATE. Antihemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM). Prescribing information [online]. Available from URL: http://www.fda.gov/cber/label/antibax072503LB.pdf [Accessed 2008 Mar 10]
- 13.Kogenate Bayer 250IU, 500IU & 1000 IU (Bio-Set) summary of product characteristics. Newbury: Bayer plc, 2007 AugGoogle Scholar
- 15.Abshire TC, Brackmann HH, Scharrer I, et al. Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy: results of a multicenter, international, clinical investigation. Thromb Haemost 2000 Jun; 83(6): 811–6PubMedGoogle Scholar
- 18.Luboshitz J, Lubetsky A, Enriquez MM, et al. Clinical evaluation of continuously infused sucrose-formulated recombinant factor VIII during surgery. Hemophilia World Congress; 2006 May 21–25; Vancouver (BC)Google Scholar
- 19.European Medicines Agency. Kogenate Bayer European public assessment report: scientific discussion [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/Kogenatebayer/101600en6.pdf [Accessed 2007 Oct 8]
- 20.Kreuz W, Gill JC, Rothschild C, et al. Full-length sucrose-formulated recombinant factor VIII for treatment of previously untreated or minimally treated young children with severe haemophilia A: results of an international clinical investigation. Thromb Haemost 2005 Mar; 93(3): 457–67PubMedGoogle Scholar
- 26.Delumeau JC. An observational study of sucrose-formulated recombinant factor VIII for Japanese patients with hemophilia A [abstract no. P-S-171]. J Thromb Haemost 2007; 5 Suppl. 2. Plus poster presented at the XXIst Congress of the International Society on Thrombosis and Haemostasis; 2007 Jul 6–12; GenevaGoogle Scholar
- 31.Maas-Enriquez M, Gorina E, Bajwa N, et al. Meta-analysis of inhibitor formation in patients with hemophilia A treated with sucrose-formulated recombinant factor VIII. XXIst Congress of the International Society on Thrombosis and Haemostasis; 2007 Jul 6–12; GenevaGoogle Scholar
- 34.World Federation of Hemophilia [online]. Available from URL: http://www.wfh.org [Accessed 2007 Oct 3]
- 37.National Hemophilia Foundation. MASAC recommendations concerning the treatment of hemophilia and other bleeding disorders (revised October 2006). MASAC document #177 [online]. Available from URL: http://www.hemophilia.org [Accessed 2007 Nov 1]
- 45.Pipe SW. Consideration in hemophilia therapy selection. Semin Hematol 2006 Apr; 43 (2 Suppl. 3): S23-7Google Scholar
- 49.National Hemophilia Foundation. MASAC recommendation 169 regarding the use of recombinant clotting factor products with respect to pathogen transmission [online]. Available from URL: http://www.hemophilia.org [Accessed 2007 Oct 5]
- 50.Parvovirus B19 transmission by heat-treated clotting factor concentrates. Transfusion (Paris) 2002 Nov; 42 (11): 1473–81Google Scholar
- 51.Association of Hemophilia Clinic Directors of Canada (AHCDC). Hemophilia and von Willebrand's disease: 2. Management. CMAJ 1995 Jul 15; 153 (2): 147–57Google Scholar
- 54.National Hemophilia Foundation. MASAC recommendation concerning prophylaxis (regular administration of clotting factor concentrate to prevent bleeding). MASAC document #170 [online]. Available from URL: http://www.hemophilia.org [Accessed 2007 Nov 7]
- 61.Woloschuk DM, Benson HA. In-vitro stability of recombinant factor VIII (Kogenate-SF) stored in an ambulatory microinfuser device [abstract no. 4021]. Blood 2000; 96 (11 Pt 2): 79BGoogle Scholar
- 62.Regan L, Chew J, Vo K, et al. Stability and sterility of sucrose-formulated recombinant factor VIII (Kogenate® FS/Bayer) for use during continuous infusion [abstract no. 4004]. Blood 2006; 108 (11 Pt 2): 79BGoogle Scholar
- 70.Butler R, Larson P, Mannix S, et al. Evaluation of user preference for a needleless factor VIII delivery device for haemophilia patients. J Outcomes Res 2004; 8: 63–78Google Scholar