1. Clinical Experience with octaplas®/octaplasLG®
Wolfgang Frenzel, M.D.
International Medical Director
Octapharma PPGmbH
Vienna, Austria
BPAC Meeting, Rockville, MD
September 20, 2012

2. Clinical Experience with octaplas®
Sources of Information
Interventional clinical studies
Non-interventional studies and retrospective data surveys
Hemovigilance data
Safety information from post-marketing reporting

3. Interventional Clinical Studies with octaplas®
Reference Design Sponsor
octaplas® Product Generation
Indications No. of Patients (octaplas®)
Focus
Control No. of Patients
Dosing
General Outcome
Inbal Prospective Octapharma
Freeze-dried
Hereditary and acquired coagulation disorders N=11
Pharmaco- kinetics, efficacy, safety
None
6-12 mL/kg
Half-lives similar to what is published for FFP
Solheim Prospective Octapharma
Open heart surgery N=20
Efficacy, safety
FFP N=20
octaplas® mean (range: 1-17) bags vs. FFP mean (range: 2-16) bags
No difference to FFP
Williamson Prospective Octapharma
Liquid, frozen
Liver disease (LD): N=13 Liver transplantation (LTX): N=12
FFP LD: N=11 LTX: N=13
LD: octaplas® median 12 (range: ) mL/kg vs. FFP median 13 (range: 11-17) mL/kg LTX: octaplas® median 12 (range: ) mL/kg vs. FFP median 13 (range: 11-17) mL/kg

4. Interventional Clinical Studies with octaplas®
Reference Design Sponsor
octaplas® Product Generation
Indications No. of Patients (octaplas®)
Focus
Control No. of Patients
Dosing
General Outcome
Haubelt Prospective Octapharma
Liquid, frozen
Open heart surgery N=36
Efficacy, safety
FFP N=31
octaplas® median (range: ) mL/kg ; FFP median (range: ) mL/kg
No difference to FFP
Santagostino Prospective Non-Octapharma
Inherited coagulation disorders N=17
Pharmaco- kinetics Efficacy, safety
None
Treatment courses median 18 (range: ) mL/kg
Recoveries & half- lives similar to what is published for FFP
Demeyere Prospective Non-Octapharma
Reversal of effect of oral anti-coagulants N=20
PCC N=18
octaplas®: 4-6 bags (200mL) per patient
No difference in INR reversal but slower than PCC; more repeated doses than with PCC
PCC Prothrombin Complex Concentrate INR International Normalized Ratio

5. Interventional Clinical Studies with octaplas®
A comparative, open-label, randomized, cross-over Phase I trial in healthy volunteers to investigate the relative efficacy, safety and tolerability of octaplasLG® vs. octaplas®
Primary objective: Efficacy (i.e. recovery of coagulation factors and haemostatic parameters)
60 subjects (per-protocol population N=43)
Exposure: octaplas® 14.9 mL/kg; octaplasLG ® 15.3 mL/kg

6. Interventional Clinical Studies with octaplas®
Set-up of Phase 1 Study

7. Interventional Clinical Studies with octaplas®
Efficacy Results Phase 1 Study
Fibrinogen
FVIII
FIX
aPTT
Protein S
Plasmin inhibitor

8. Interventional Clinical Studies with octaplas®
General Outcomes
No difference between FFP and octaplas® in terms of efficacy
No difference between FFP and octaplas® in terms of safety
No difference between octaplas® and octaplasLG ® in terms of efficacy

9. Non-Interventional Studies and Retrospective Surveys
Reference Design Sponsor
octaplas® Product Generation
Indications No. of Patients (octaplas®)
Control No. of Patients
Dosing
General Outcome
Hellstern Prospective Octapharma
Liquid, frozen
Disseminated Intravascular Coagulation N=30
None
octaplas® mean 5.2 ± mL/kg
Satisfying efficacy
Chekrizowa Retrospective Non-Octapharma
Neonatal complications, obstetric emergencies, liver disease N=104
Neonates: mean mL/kg; Obstetrics: mean 15 ± 8 mL/kg; liver disease: 38±42 mL/kg (children); ±3.4 mL/kg (adults)
Satisfying efficacy and tolerability; no unexpected clinical outcomes
Scully Retrospective Non-Octapharma
TTP N=21
CSP N=12
octaplas® 34.1 L per episode CSP 29.0 L
No difference between products; octaplas® was better tolerated
Edel Retrospective Non-Octapharma
TTP N=8 (7 with severe ADAMTS13 deficiency)
Daily plasma volumes per exchange
Platelet counts above x 109/L achieved
TTP Thrombotic Thrombocytopenic Purpura CSP Cryosupernatant Plasma

10. Observational Study conducted in Germany
Non-Interventional, Prospective Study
Observational Study conducted in Germany
Sequence I: 65 patients on octaplas®
Sequence II: 60 patients on octaplasLG®
Under routine clinical conditions

11. Non-Interventional, Prospective Study
Efficacy Results

12. Hemovigilance Data Bags of octaplas® 173,664 267,000
177,986
2,621
239,359
Total 860,630
United Kingdom: 3 hemovigilance reports covering 3 years
Austria: 5 hemovigilance reports covering 5 years
Norway: 4 hemovigilance reports covering 4 years
Sweden: published experience from 1 site, covering 2 years
Finland: publication; Finnish Red Cross, covering 7 years

13. Hemovigilance Data United Kingdom (SHOT Reports) 2009 FFP/MB 306.740
Year
Bags
AEs
95% CI
FNHTR
Allergic
Allergic/ febrile
Anaphylactic
Hypotension
TRALI
Others
2009 FFP/MB 44 5 21 9 6 2 1
2009 octaplas®
52.963
2010 FFP/MB 45 4 26 3
2010 octaplas®
57.487
2011 FFP/MB 43 25 10
2011 octaplas®
63.214
Total '09-'11 FFP/MB
132 72 28 11
1 per ... NA
6.840
90.283
12.539
32.244
82.075
Total '09-'11 Octaplas
28.944
57.888
> 173'664
86.832
AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction MB Methylene Blue Plasma

14. Hemovigilance Data Austria (Hämovigilanz Jahresberichte) Year Bags AEs
95% CI
FNHTR
Allergic
TRALI
Others
2003 FFP
26.800 16 1 11 4
2003 octaplas®
57.700 7 3
2004 FFP
23.900 25 2 19
2004 octaplas®
55.000
2005 FFP
23.100 8
2005 octaplas®
50.100
2006 FFP
23.500 17 14
2006 octaplas®
52.400
2009 FFP
15.300 24 21
2009 octaplas
51.800
Total '03-'06+09 FFP 93 73 12
1 per ... NA
1.211
16.086
1.542
9.383
Total '03-'06+09 Octaplas
22.250
66.750
33.375
> 267'000
AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction

15. Lifethreatening /serious
Hemovigilance Data
Norway (TROLL Reports) – all octaplas®
Year
Bags
AEs
Lifethreatening /serious
Less or non-serious
TRALI
Cardio-vascular
Anaphylactoid
Allergic
FNHTR
Others
2007
39.867 15 1 14 6 2
2008
47.690 13 4 3
2009
45.344 11 5
2010
45.085
Total '07-'10 45 43 19 9
1 per ... NA
3.955
88.993
4.139
> 177'986
29.664
9.368
16.181
19.776
AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction

16. Life threatening/ serious
Hemovigilance Data
Experience from Sweden (Vaara 2010)
Year
Bags
AEs
95% CI
Life threatening/ serious
Less or non-serious
FFP
1.135 19 5 14
octaplas®
2.621
Total FFP
1 per ... NA 60
227 81
Total Octaplas
> 2'621

17. Hemovigilance Data Experience from Finland (Krusius 2012) Year Bags
Serious AEs
95% CI
TRALI
FFP
90.372 22 5
octaplas® 14
Total '05-'11 FFP
1 per ... NA
4.108
18.074
Total '05-'11 Octaplas
17.097
> 239'359

18. Post-Authorization Safety (Pharmacovigilance) Data octaplas®
Sales Figures 1992 to 2011 (trade sales & contract work)
In total 7’553’122 bags, thereof 142’110 octaplasLG® in Germany

19. Post-Authorization Safety (Pharmacovigilance) Data
Overview on Non-Serious Case Reports

20. Post-Authorization Safety (Pharmacovigilance) Data
Overview on Serious Case Reports

21. Clinical Experience with octaplas®
Summary of Available Clinical Information
Interventional clinical studies: 7 studies, 177 patients
Non-interventional studies and retrospective data surveys: 5 studies, 288 patients
Hemovigilance data: covering 21 years documented in 14 reports of 5 countries, covering 860,000 bags of octaplas®
Safety information from post-marketing reporting: from more than 7.6 million bags of octaplas® corresponding to about 2 million treatments since 1992