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Sucrose-Formulated Octocog Alfa

A Review of its Use in Patients with Haemophilia A

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Summary

Abstract

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.

Pharmacological Properties

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).

Clinical Efficacy

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.

Tolerability

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%.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Authors and Affiliations

  1. Wolters Kluwer Health ¦ Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754 Auckland, New Zealand

    James E. Frampton & Antona J. Wagstaff

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    James E. Frampton & Antona J. Wagstaff

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Correspondence to James E. Frampton.

Additional information

Various sections of the manuscript reviewed by: L.M. Aledort, Mount Sinai School of Medicine, New York, New York, USA; J.M. Lusher, Division of Hematology/Oncology, Department of Pediatrics, Children’s Hospital of Michigan, Detroit, Michigan, USA; S.W. Pipe, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan, USA; I. Scharrer, Department of Hematology, University of Mainz, Mainz, Germany; J.M. Stachnik, Department of Pharmacy Practice, University of Illinois Medical Center at Chicago, Chicago, Illinois, USA; R. Yang, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘octocog alfa’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Wolters Kluwer Health | Adis). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘recombinant coagulation factor-VIII’ or ‘rFVIII’ or ‘octocog alfa’. Searches were last updated 7 March 2008.

Selection: Studies in patients with haemophila who received octocog alfa formulated with sucrose in clinical trials. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Octocog alfa, recombinant factor VIII, haemophilia A, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Frampton, J.E., Wagstaff, A.J. Sucrose-Formulated Octocog Alfa. Drugs 68, 839–853 (2008). https://doi.org/10.2165/00003495-200868060-00007

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