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

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

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

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 log10

Other process steps provide additional safety

*CPMP/BWP/268/95, 1996. CPMP/BWP/269/95 rev 3., 2001

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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

WFH Bangkok 2004

Octanate – Pharmacokinetics

Parameter Octanate

(Study 1, n = 10)

Octanate

(Study 2, n = 14)

Half-Life

(t ½ , h)14.3 ± 4.01 12.6 ± 3.03

Recovery

(IU/dl per IU/kg)2.4 ± 0.36 2.4 ± 0.25

Area Under the Curve (AUC, %.h.IU-1.kg)

45.5 ± 17.20 33.4 ± 8.50

Mean Residence Time

(MRT, h)19.6 ± 6.05 16.6 ± 3.73

Clearance

(CL, ml.h-1.kg)2.6 ± 1.21 3.2 ± 0.88

WFH Bangkok 2004

Octanate – Clinical Efficacy

95.3 % of All Bleeding Episodes Resolved Within 3 Days

0%

25%

50%

75%

100%

Total (N=1,096) AVE-401 (N=167) AVE-402 (N=374) AVE-406 (N=213) AVE-407 (N=342)

Re

so

lve

d W

ith

in (

%)

1 day

2 day

3 day

4 day

5 day

6 day

7 day

> 5 days

No. Bleeds 1096 (Total) 167 (Study 1) 374 (Study 2) 213 (Study 3) 342 (Study 4)

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 250 5 ml

Octanate 500 10 ml

Octanate 1000 10 ml