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WFH Bangkok 2004 Octanate – Factor VIII with the Safety Factor VWF High Purity Plasma-Derived Factor VIII Double Virus Inactivated Haemophilia A Treatment.

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Presentation on theme: "WFH Bangkok 2004 Octanate – Factor VIII with the Safety Factor VWF High Purity Plasma-Derived Factor VIII Double Virus Inactivated Haemophilia A Treatment."— Presentation transcript:

1 WFH Bangkok 2004 Octanate – Factor VIII with the Safety Factor VWF High Purity Plasma-Derived Factor VIII Double Virus Inactivated Haemophilia A Treatment and Prophylaxis

2 WFH Bangkok 2004 Octanate at a Glance  Physiological factor VIII Naturally stabilised with VWF Highly purified Non denatured  Extensive clinical use Safe Effective Well-tolerated  State-of-the-art virus safety High quality starting plasma Double virus inactivation: Solvent / Detergent (S/D) treatment Short duration dry heating, 100 °C, 30 min  Convenient handling Small injection volume Easy documentation

3 WFH Bangkok 2004 Octanate Manufacturing Process Cryoprecipitate Resuspension in ethanol-heparin Aluminium hydroxide addition Adsorption and precipitation S/D virus inactivation Ion exchange chromatography Ultrafiltration, diafiltration Sterile filtration, filling Lyophilisation, vial closure Terminal dry heating, 100 °C, 30 min OCTANATE

4 WFH Bangkok 2004 Resuspension of cryoprecipitate in alcohol and heparin is the first step to precipitating and removing fibrinogen Aluminium hydroxide (2.5 %) addition precipitates factors of the prothrombin complex, limiting enzymatic activation of the factor VIII, as well as precipitating fibrinogen S/D treatment (0.3 % TNBP, 1 % Tween 80) effectively inactivates lipid-coated viruses Ion exchange chromatography achieves high purification of the factor VIII-VWF complex and removal of the S/D reagents Terminal dry heating at 100 °C for 30 minutes inactivates both enveloped and non enveloped viruses, adding a further level of safety Octanate Manufacturing Process

5 WFH Bangkok 2004 Octanate – Viral Safety: Conclusion Octanate fulfils all current requirements for virus safety set out by regulatory bodies, such as the Committee for Proprietary Medicinal Products* Two effective steps against lipid enveloped viruses One effective step against non enveloped viruses A combination of methods based on different principles of action Inactivation procedures with a high safety margin Rapid virus inactivation Robustness in the event of process variations Validation of each step with a wide variety of viruses An individual step efficacy equivalent to 4 log 10 Other process steps provide additional safety *CPMP/BWP/268/95, CPMP/BWP/269/95 rev 3., 2001

6 WFH Bangkok 2004 Octanate – Double Virus Inactivated Enveloped VirusesNon Enveloped Viruses Virus Genome HIV-1 Human Immuno- deficiency Virus RNA SBV Sindbis Virus RNA BVDV Bovine Viral Diarrhoea Virus RNA HSV-1 Herpes Simplex Virus DNA HAV Hepatitis A Virus RNA REO Reovirus RNA StepVirus Reduction (log 10 ) S/D Treatment> 5.3> 7.4> 6.8  Dry Heat> 6.6> 6.5> 6.6> 4.0> 7.0> 7.2 Sum Inactivation> 11.9> 13.9> 13.4> 10.6> 7.0> 7.2 Other Process Steps > 1.6 Global Reduction> 11.9> 13.9> 13.4> 13.8> 10.6> 8.8

7 WFH Bangkok 2004 Importance of von Willebrand Factor Biosynthesis of factor VIII VWF imparts correct factor VIII structure and secretion Stabilisation of factor VIII Protects against unwanted activation and degradation Transport of factor VIII Directs factor VIII to the site of injury Octanate – Physiologically Stabilised with VWF

8 WFH Bangkok 2004 Octanate – Physiologically Stabilised with VWF If Octanate factor VIII-VWF complex ( ) is mixed with free factor VIII ( ), it is immediately bound by VWF and co-elutes as a single-peak complex ( ) in Size Exclusion Chromatography This shows that:  VWF posesses high binding capacity for F VIII  VWF effectively stabilises F VIII  The FVIII-VWF interaction in Octanate is intact Octanate VWF Binding Capacity for Factor VIII

9 WFH Bangkok 2004 Octanate is stabilised naturally by von Willebrand Factor –VWF stabilisation avoids the use of albumin stabiliser –Patients receive less foreign protein –FVIII protected by VWF may be less immunogenic –PUPs tend to develop a lower incidence of inhibitors –Therapy of patients with inhibitors can be more effective Octanate – Physiologically Stabilised with VWF

10 WFH Bangkok 2004 Octanate – Non Denatured and Physiologically Active Intact Phospholipid Binding Surface Plasmon Resonance Method (BIACORE) ( ) Octanate ( ) Denatured factor VIII (70 °C, 2 h, in solution) ( ) Negative control bovine serum albumin If Octanate is brought into contact with a phospholipid- coated chip, factor VIII will bind to the phospholipid The factor VIII binding curve is typical for non denatured factor VIII

11 WFH Bangkok 2004 Octanate – Pharmacokinetics Parameter Octanate (Study 1, n = 10) Octanate (Study 2, n = 14) Half-Life (t ½, h) 14.3 ± ± 3.03 Recovery (IU/dl per IU/kg) 2.4 ± ± 0.25 Area Under the Curve (AUC, %.h.IU -1.kg) 45.5 ± ± 8.50 Mean Residence Time (MRT, h) 19.6 ± ± 3.73 Clearance (CL, ml.h -1.kg) 2.6 ± ± 0.88

12 WFH Bangkok 2004 Octanate – Pharmacokinetics Octanate shows good half-life and recovery results In four completed studies, 62 patients were treated and 3.8 million IU of Octanate administered In studies lasting for at least 6 months, the mean number of exposure days per patient was 36.4 After 6 months, there were no statistical deviations of any pharmacokinetic parameters There was no inhibitor development

13 WFH Bangkok 2004 Octanate – Clinical Efficacy 95.3 % of All Bleeding Episodes Resolved Within 3 Days No. Bleeds 1096 (Total) 167 (Study 1) 374 (Study 2) 213 (Study 3) 342 (Study 4)

14 WFH Bangkok 2004 Octanate at a Glance – In Daily Clinical Use  Clinical safety and efficacy No inhibitors No virus transmissions Very well tolerated Very good efficacy Successful use in surgery, and in continuous infusion  Convenient handling Small injection volume Easy documentation Pull-off labels Dissolves rapidly Complete application set  Presentation  Storage and shelf-life 24 months shelf-life at + 4 °C to + 8 °C. Do not freeze. Protect from light Package Size (IU)Injection Volume Octanate 2505 ml Octanate ml Octanate ml


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