Clinical Experience with octaplas®/octaplasLG®

Wolfgang Frenzel, M.D.

International Medical Director

Octapharma PPGmbH

Vienna, Austria

BPAC Meeting, Rockville, MDSeptember 20, 2012

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Interventional clinical studies

Non-interventional studies and retrospective data surveys

Hemovigilance data

Safety information from post-marketing reporting

Sources of Information

Clinical Experience with octaplas®

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ReferenceDesign

Sponsor

octaplas®

Product Generation

IndicationsNo. of Patients

(octaplas®)Focus

ControlNo. of

PatientsDosing General Outcome

Inbal 1993ProspectiveOctapharma

Freeze-dried

Hereditary and acquired coagulation disordersN=11

Pharmaco-kinetics, efficacy, safety

None 6-12 mL/kgHalf-lives similar to what is published for FFP

Solheim 1993ProspectiveOctapharma

Freeze-driedOpen heart surgeryN=20

Efficacy, safety

FFPN=20

octaplas® mean 3.5 (range: 1-17) bags vs. FFP mean 4.1 (range: 2-16) bags

No difference to FFP

Williamson 1999ProspectiveOctapharma

Liquid, frozen

Liver disease (LD): N=13Liver transplantation (LTX): N=12

Efficacy, safety

FFPLD: N=11LTX: N=13

LD: octaplas® median 12 (range: 11-15) mL/kg vs. FFP median 13 (range: 11-17) mL/kgLTX: octaplas® median 12 (range: 11-15) mL/kg vs. FFP median 13 (range: 11-17) mL/kg

No difference to FFP

Interventional Clinical Studies with octaplas®

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ReferenceDesign

Sponsor

octaplas®

Product Generation

IndicationsNo. of Patients

(octaplas®)Focus

ControlNo. of

PatientsDosing General Outcome

Haubelt 2002ProspectiveOctapharma

Liquid, frozen

Open heart surgeryN=36

Efficacy, safety

FFPN=31

octaplas® median 8.5 (range: 5.5-14.2) mL/kg ;FFP median 8.5 (range: 5.5-12.2) mL/kg

No difference to FFP

Santagostino 2006ProspectiveNon-Octapharma

Liquid, frozen

Inherited coagulation disordersN=17

Pharmaco-kineticsEfficacy, safety

NoneTreatment courses median 18 (range: 6-29) mL/kg

Recoveries & half-lives similar to what is published for FFP

Demeyere 2010ProspectiveNon-Octapharma

Liquid, frozen

Reversal of effect of oral anti-coagulantsN=20

Efficacy, safety

PCCN=18

octaplas®: 4-6 bags (200mL) per patient

No difference in INR reversal but slower than PCC; more repeated doses than with PCC

Interventional Clinical Studies with octaplas®

PCC Prothrombin Complex ConcentrateINR International Normalized Ratio

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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

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®

Interventional Clinical Studies with octaplas®

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Set-up of Phase 1 Study

Interventional Clinical Studies with octaplas®

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Fibrinogen

Plasmin inhibitor

FIX

aPTTProtein S

FVIII

Efficacy Results Phase 1 Study

Interventional Clinical Studies with octaplas®

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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

General Outcomes

Interventional Clinical Studies with octaplas®

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ReferenceDesign

Sponsor

octaplas® Product

Generation

IndicationsNo. of Patients

(octaplas®)

ControlNo. of

PatientsDosing General Outcome

Hellstern 1993ProspectiveOctapharma

Liquid, frozen

Disseminated Intravascular CoagulationN=30

Noneoctaplas® mean 5.2 ± 1.1 mL/kg

Satisfying efficacy

Chekrizowa 2006RetrospectiveNon-Octapharma

Liquid, frozen

Neonatal complications, obstetric emergencies, liver diseaseN=104

None

Neonates: mean 18.4 mL/kg;Obstetrics: mean15 ± 8 mL/kg;liver disease: 38±42 mL/kg (children);10.2±3.4 mL/kg (adults)

Satisfying efficacy and tolerability; no unexpected clinical outcomes

Scully 2007RetrospectiveNon-Octapharma

Liquid, frozen

TTPN=21

CSPN=12

octaplas® 34.1 L per episode CSP 29.0 L

No difference between products; octaplas® was better tolerated

Edel 2010RetrospectiveNon-Octapharma

Liquid, frozen

TTP N=8 (7 with severe ADAMTS13 deficiency)

NoneDaily 1-1.5 plasma volumes per exchange

Platelet counts above 150 x 109/L achieved

Non-Interventional Studies and Retrospective Surveys

TTP Thrombotic Thrombocytopenic PurpuraCSP Cryosupernatant Plasma

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Sequence I: 65 patients on octaplas®

Sequence II: 60 patients on octaplasLG®

Under routine clinical conditions

Observational Study conducted in Germany

Primary Indications

plasma exchange

peri- / intraoperative use

consumptive coagulopathy / DIC

non-surgical bleeding

other

Non-Interventional, Prospective Study

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Efficacy Results

64/98%

1

57/95%

3

0

10

20

30

40

50

60

70

Successful Not succesful

octaplas®

octaplasLG®

Non-Interventional, Prospective Study

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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

Hemovigilance Data

Bags ofoctaplas®

173,664

267,000

177,986

2,621

239,359

Total 860,630

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Year Bags AEs 95% CI FNHTR AllergicAllergic/febrile

Anaphylactic Hypotension TRALI Others

2009 FFP/MB 306.740 44 30.3-56.8 5 21 0 9 6 2 1

2009 octaplas® 52.963 2 0.2-7.2 0 1 0 1 0 0 0

2010 FFP/MB 292.884 45 32.0-59.1 4 26 2 9 3 1 0

2010 octaplas® 57.487 1 0.0-5.6 0 1 0 0 0 0 0

2011 FFP/MB 303.202 43 30.3-56.8 1 25 2 10 2 1 2

2011 octaplas® 63.214 3 0.6-8.8 1 1 0 1 0 0 0

Total '09-'11 FFP/MB

902.826 132 106.8-152.2 10 72 4 28 11 4 3

1 per ... NA 6.840 NA 90.283 12.539 225.707 32.244 82.075 225.707 300.942

Total '09-'11 Octaplas

173.664 6 2.2-13.1 1 3 0 2 0 0 0

1 per ... NA 28.944 NA 173.664 57.888 > 173'664 86.832 > 173'664 > 173'664 > 173'664

United Kingdom (SHOT Reports)

Hemovigilance Data

AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion ReactionMB Methylene Blue Plasma

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Year Bags AEs 95% CI FNHTR Allergic TRALI Others

2003 FFP 26.800 16 9.1-26.0 1 11 0 4

2003 octaplas® 57.700 7 2.8-14.4 3 4 0 0

2004 FFP 23.900 25 16.2-36.9 2 19 0 4

2004 octaplas® 55.000 1 0.0-5.6 0 1 0 0

2005 FFP 23.100 11 5.5-19.7 1 8 0 2

2005 octaplas® 50.100 0 0.0-3.7 0 0 0 0

2006 FFP 23.500 17 9.9-27.2 1 14 0 2

2006 octaplas® 52.400 2 0.2-7.2 0 2 0 0

2009 FFP 15.300 24 15.4-35.7 2 21 1 0

2009 octaplas 51.800 2 0.2-7.2 1 1 0 0

Total '03-'06+09 FFP 112.600 93 75.1-113.9 7 73 1 12

1 per ... NA 1.211 NA 16.086 1.542 112.600 9.383

Total '03-'06+09 Octaplas 267.000 12 6.2-21.0 4 8 0 0

1 per ... NA 22.250 NA 66.750 33.375 > 267'000 > 267'000

Austria (Hämovigilanz Jahresberichte)

Hemovigilance Data

AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction

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Year Bags AEsLifethreatening

/seriousLess or

non-seriousTRALI

Cardio-vascular

Anaphylactoid Allergic FNHTR Others

2007 39.867 15 1 14 0 0 1 6 6 2

2008 47.690 14 1 13 0 0 4 6 3 1

2009 45.344 11 0 11 0 0 1 3 2 5

2010 45.085 5 0 5 0 0 0 4 0 1

Total '07-'10 177.986 45 2 43 0 0 6 19 11 9

1 per ... NA 3.955 88.993 4.139 > 177'986 > 177'986 29.664 9.368 16.181 19.776

Norway (TROLL Reports) – all octaplas®

Hemovigilance Data

AEs Adverse Events FNHTR Febrile Non-Hemolytic Transfusion Reaction

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Year Bags AEs 95% CI Life threatening/ serious

Less or non-serious

FFP 1.135 19 11.5-29.5 5 14

octaplas® 2.621 0 0.0-3.7 0 0

Total FFP 1.135 19 11.5-29.5 5 14

1 per ... NA 60 NA 227 81

Total Octaplas 2.621 0 0.0-3.7 0 0

1 per ... NA > 2'621 NA > 2'621 > 2'621

Experience from Sweden (Vaara 2010)

Hemovigilance Data

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Year Bags Serious AEs 95% CI TRALI 95% CI

FFP 90.372 22 13.8-33.3 5 1.6-11.7

octaplas® 239.359 14 0.6-8.8 0 0.0-3.7

Total '05-'11 FFP 90.372 22 13.8-33.3 5 1.6-11.7

1 per ... NA 4.108 NA 18.074 NA

Total '05-'11 Octaplas 239.359 14 0.6-8.8 0 0.0-3.7

1 per ... NA 17.097 NA > 239'359 NA

Experience from Finland (Krusius 2012)

Hemovigilance Data

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Sales Figures 1992 to 2011 (trade sales & contract work)

Post-Authorization Safety (Pharmacovigilance) Data octaplas®

In total 7’553’122 bags, thereof 142’110 octaplasLG® in Germany

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Overview on Non-Serious Case Reports

Post-Authorization Safety (Pharmacovigilance) Data

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Overview on Serious Case Reports

Post-Authorization Safety (Pharmacovigilance) Data

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Interventional clinical studies: 7 studies, 177 patients

Non-interventional studies and retrospective data surveys:5 studies, 288 patients

Hemovigilance data: covering 21 years documented in14 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

Summary of Available Clinical Information

Clinical Experience with octaplas®