PRODUCT INN REFERENCE AUTHORIZATION

Omnitropesomatropin

Genotropin 12/04/2006

Valtropin (W/D) Humatrope 24/04/2006

AbseamedBinocrit

Epoetina alfa hexalepoetin alpha

Eprex28/08/2007

RetacritSilapo

epoetina zeta 18/12/2007

BiograstimFilgrastim

ratiopharm WPRatiograstimTevagrastim filgrastim Neupogen

15/09/2008

Filgrastim HexalZarzio

06/02/2009

Nivestim 08/06/2010

Grastofil 18/10/2013

Ovaleap follitropin alpha Gonal-F 27/09/2013

InflectraRemsima

infliximab Remicade 10/09/2013

follitropin Gonal-F Under review

Insulin glargine Lantus Under review

trastuzumab Herceptin Not submitted yet

1877: A dead heat at the Oxford Vs Cambridge University Boat Race in 1877

Competizione; accesso al mercato; risorse per migliorare

Gare in concorrenza diretta hanno portato ad un abbassamento dei prezzi di oltre il 75% rispetto al periodo precedente la scadenza brevettuale

Overview of currently approved biosimilar products in Europe*

1. EMA. European Public Assessment Reports. Biosimilar Medicines Authorized by the Agency [website]. Accessed Feb 5, 2014; 2. FDA. Information for Consumers – Biosimilars [website]. Accessed Feb 5, 2014

201320102009200820072006

Biograstim®

Ratiograstim®

Tevagrastim®

Omnitrope®

Abseamed®

Binocrit®

Epoetin Alfa Hexal®

Retacrit®

Silapo®

Zarzio® Nivestim®

Inflectra®

Remsima®

Ovaleap®

Filgrastim-Hexal®

Human growth hormone (somatropin)

Erythropoietin (epoetin alfa, zeta)

Granulocyte colony-stimulating factor

Follicule-stimulating hormone (follitropin alfa)

*None FDA-approved as of February 20142

FDA, Food and Drug Administration

Grastofil®

Anti-TNF- monoclonal antibody (infliximab)

PRODUCT INN REFERENCE AUTHORIZATION

Omnitropesomatropin

Genotropin 12/04/2006

Valtropin (W/D) Humatrope 24/04/2006

AbseamedBinocrit

Epoetina alfa hexalepoetin alpha

Eprex28/08/2007

RetacritSilapo

epoetina zeta 18/12/2007

BiograstimFilgrastim

ratiopharm WPRatiograstimTevagrastim filgrastim Neupogen

15/09/2008

Filgrastim HexalZarzio

06/02/2009

Nivestim 08/06/2010

Grastofil 18/10/2013

Ovaleap follitropin alpha Gonal-F 27/09/2013

InflectraRemsima

infliximab Remicade 10/09/2013

follitropin Gonal-F Under review

Insulin glargine Lantus Under review

trastuzumab Herceptin Not submitted yet

Remicade: ATTRACT1 CT-P13: PLANETRA2

1O Endpoint Results

EfficacyACR20 at wk 30 (PP)ACR20 at wk 30 (ITT)ACR20 at wk 54Mean change from baseline (vdH-S Total)

Pbo +

MTX

--20%17%6.9

R® 3

mg/kg

(q8wk)

--50%42%1.3

R® 10

mg/kg

(q8wk)

--52%59%0.2

CT-P13

60.9%73.4%----

IFX 3 mg

58.6%69.7%----

2O Endpoint Results

EfficacyACR50 at wk 30ACR70 at wk 30

5%0%

27% 8%

31% 18%

42.3% 20.2%

40.6% 17.9%

Adverse Events

SafetyStudy-Related AEsRelated infection>=1 Infusion reactionTuberculosisSerious adverse eventsSerious infectionsSerious infusion reactionsAntinuclear antibodiesAntibodies against doublestranded DNA

-- -- -- -- 21% 8% 0% 26% 0%

-- -- -- -- 11% 2% 0% 68% 10%

-- -- -- -- 20% 8% 0% 62% 10%

35.2% 15.3% 5% 3 pts -- -- -- -- --

35.9% 16.9% 6% 1 pt -- -- -- -- --

1. Remicade: Label Full Prescribing Information, P3 Trial (NCT00269867), Journal Article Lipsky et al, 2000. N Engl J Med. 2000 Nov 30;343(22):1594-6022. CT-P13: PLANETRA P3 Trial (NCT01217086), Abstract 1: EULAR12-2238, Abstract 2: EULAR12-2547……..P’Kinetic data for CT-P13 is reported for patients with ankylosing spondylitis

INDICAZIONI: rheumatoid arthritis, adult Crohn’s disease, paediatric Crohn’s disease,

ulcerative colitis, paediatric ulcerative colitis, ankylosing spondylitis, psoriatic arthritis

and psoriasis

Gonal-F Ovaleap

patients 145 152

Number of oocytes retrievedprimary endpoint

12.0 + 6.8 12.2 + 6.2

Total dose (S.E.) 1614 + 484 1539 + 495

# pts with dose increase 43.2% 35.9%

# patients with dose decreases

15.1% 15.0%

Ongoing pregnancy rate 0.34 0.28

Lo studio del biosimilare FSHSetting: Infertile ovulatory women undergoing ART

PRODUCT INN REFERENCE AUTHORIZATION

Omnitropesomatropin

Genotropin 12/04/2006

Valtropin (W/D) Humatrope 24/04/2006

AbseamedBinocrit

Epoetina alfa hexalepoetin alpha

Eprex28/08/2007

RetacritSilapo

epoetina zeta 18/12/2007

BiograstimFilgrastim

ratiopharm WPRatiograstimTevagrastim filgrastim Neupogen

15/09/2008

Filgrastim HexalZarzio

06/02/2009

Nivestim 08/06/2010

Grastofil 18/10/2013

Ovaleap follitropin alpha Gonal-F 27/09/2013

InflectraRemsima

infliximab Remicade 10/09/2013

follitropin Gonal-F Under review

Insulin glargine Lantus Under review

trastuzumab Herceptin Not submitted yet

What is a relevant end-point for equivalence and are all extrapolations equal??

Primi 20 principi attivi per consumo(a valore)

Ran

k Consumi a valore 2013(Migliaia di€)

Variazioni %2013 vs 2012

Quota di mercato

ITALIA 8.585.043 5,3% 100,0%

→ TRASTUZUMAB 232.484 -0,4% 2,7%

↑ ETANERCEPT 214.272 3,2% 2,5%

↑ ADALIMUMAB 212.804 12,1% 2,5%

→ EPOETINA ALFA 180.113 -0,2% 2,1%

↑ INTERFERONE BETA 1A 178.984 3,3% 2,1%

↑ IMMUNOGLOBULINA UMANA NORMALE 177.906 4,8% 2,1%

→ RITUXIMAB 174.078 1,0% 2,0%

↓ IMATINIB MESILATO 159.812 -1,3% 1,9%

→ OCTOCOG ALFA (FATTORE VII COAGULAZ) 135.226 -0,2% 1,6%

↑ BEVACIZUMAB 133.856 4,7% 1,6%

↓ EMTRICITABINA TENOFOVIR DISOPROXIL 128.795 -1,1% 1,5%

↑ LENALIDOMIDE 124.082 6,5% 1,4%

↑ EFAVIRENZ EMTRICITABINA TENOFOVIR DI 108.511 2,3% 1,3%

↑ RANIBIZUMAB 106.675 85,7% 1,2%

↑ INFLIXIMAB 103.859 1,1% 1,2%

→ PEMETREXED DISODICO 89.940 -0,5% 1,0%

↓ ALBUMINA UMANA 84.048 -7,4% 1,0%

↑ ENOXAPARINA SODICA 83.720 10,7% 1,0%

↑ PACLITAXEL 83.215 6,4% 1,0%

↑ BORTEZOMIB 78.358 5,9% 0,9%

TOTALE PRIMI 20 2.790.738 4,4% 32,5%

TOTALE ALTRI 5.794.305 5,7% 67,5%

Ongoing phase III trials with Anti-HER2 ABs

• Adjuvant:

- Pertuzumab + Trastuzumab vs Trastuzumab (Aphinity)

- Trastuzumab Emtansine vs Trastuzumab + Pertuzumab (Kaitlin)

- Trastuzumab Emtansine vs Trastuzumab (no pCR after neoadjuvant therapy) (Katherine)

• Neo/adjuvant:

- Taxane + Pertuzumab + Trastuzumab vs Trastuzumab Emtansine + Pertuzumab (Kristine)

• Advanced:

- 1° line: Trastuzumab + Taxane vs Trastuzumab Emtansine vs Trastuzumab Emtansine + Pertuzumab (Marianne)

- 2°line: Pertuzumab + TPC vs TPC (Traetment of Phisician Choice)

Clinical complexity may not correlate only with molecular structure

Clinical experience (PASS, PAES, submissions of PSUR, use in Europe, scientific evidence of prescriptive behaviors) or ad

hoc studies modify the clinical complexity