Hemophilia

Kogenate FS^® (Antihemophilic Factor [Recombinant]) is approved for use in adults and children with hemophilia A,¹ a genetic blood disorder characterized by reduced levels of clotting factor VIII (FVIII).² Individuals with hemophilia A have impaired blood clotting that may result in excessive bleeding.^2,3 Internal bleeding into joints and muscles is typical in these patients and can lead to a disabling arthropathy.⁴

Kogenate FS was developed and is commercialized by Bayer and was approved by the US Food and Drug Administration in 1993.¹ It is also approved for use in the European Union.⁵ Kogenate FS is indicated for the control and prevention of episodes of bleeding in patients with hemophilia A, and for perioperative management, to reduce the risk for bleeding.¹

Mechanism of Action and Use

Kogenate FS is a native, full-length FVIII molecule (octocog alfa) produced with recombinant DNA technology from a baby hamster kidney (BHK) cell line.^1,4,5 The resultant glycoprotein contains multiple peptides and has activity similar to that of the FVIII in human plasma.¹ When administered, Kogenate FS temporarily replaces the missing FVIII, promoting adequate hemostasis.⁵ Kogenate FS is purified and formulated without the addition of human-derived plasma proteins (eg, albumin) and with sucrose stabilization.⁴ The manufacturing process of this replacement therapy also includes an additional step of viral inactivation.^1,6

Kogenate FS is formulated for intravenous administration after reconstitution and is available as a lyophilized powder in single-use vials.¹ The dosage and duration of treatment vary according to disease severity and the extent and type of bleeding. It is recommended that a major episode of bleeding be initially treated with 40 to 50 IU of Kogenate FS per kilogram.¹

The most common adverse reactions to Kogenate FS are inhibitor development in previously untreated and minimally treated patients, infusion site reactions, and hypersensitivity reactions. A device may be surgically placed under the skin to facilitate the administration of Kogenate FS when frequent injections are required; however, this procedure may lead to central venous access device infections.¹

Kogenate FS is contraindicated in patients who are allergic to hamster protein or to any of the other constituents of the commercialized formulation.¹

Get full prescribing information for Kogenate FS at MPR

Efficacy and Safety in Clinical Trials

The safety and efficacy of Kogenate FS were demonstrated in an initial clinical trial that enrolled previously treated patients with severe hemophilia A.⁶ The study compared the efficacy of Kogenate FS in 71 participants with that of a previously licensed Kogenate product manufactured without sucrose stabilization. Kogenate FS was shown to be well tolerated, with no significant side effects reported and with excellent control of bleeding.⁶ 

Following the phase 3 SPINART trial (NCT00623480), Kogenate FS was approved for routine prophylaxis in patients with hemophilia A. This 3-year open-label, randomized, controlled, parallel-group trial enrolled 84 previously treated patients with severe hemophilia A between 12 and 50 years old.⁷ Reported results of the trial indicated a significant reduction in the median number of episodes of bleeding when the use of Kogenate FS as prophylaxis was compared with its use as on-demand treatment. Inhibitor development was not observed, and no adverse effects of the treatment were reported.⁷ The effect of late prophylaxis with Kogenate FS on joint structure was also reported. The use of Kogenate FS resulted in a decrease of bleeding and pain and promoted a better quality of life; however, the progression of structural arthropathy was not reduced. These results point to the importance of initiating prophylaxis with Kogenate FS before joint bleeding occurs and before permanent arthropathy develops.⁸

References

1. KOGENATE FS (antihemophilic factor [recombinant], formulated with sucrose). Prescribing information. Revised December 2019. Accessed December 30, 2021.

2. Hemophilia A. National Organization for Rare Disorders (NORD). Accessed December 30, 2021.

3. Hemophilia A. National Hemophilia Foundation. Accessed December 30, 2021.

4. Lusher J, Chitlur M, Kogenate^® FS: antihemophilic factor rFVIII-FS. Therapy 2006;3(6):699-708. doi:10.1586/14750708.3.6.699

5. Kogenate Bayer. European Medicines Agency. Accessed December 30, 2021.

6. 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–International Kogenate-FS Study Group. Thromb Haemost. 2000;83(6):811-816.

7. Manco-Johnson MJ, Kempton CL, Reding MT, Lissitchkov T, et al. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013;11(6):1119-27. doi:10.1111/jth.12202. Erratum in: J Thromb Haemost. 2014;12(1):119-122.

8. Manco-Johnson MJ, Lundin B, Funk S, et al. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017;15(11):2115-2124. doi:10.1111/jth.13811

Reviewed by Hasan Avcu, MD, on 1/31/2022.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.