1. Prof. Karina JAHNZ-RÓŻYK MD, Ph.D. ACCESS TO THE BIOLOGICAL TREATMENT IN POLAND ISPOR POLAND CHAPTER, ATLANTA 2010

2. Poland - general info 8 th country in Europe by area: 312,000 km 2 Republic of Poland 6 th country in Europe by population: 38,500,696 (July 2008 est.) 7 th country by size of pharmaceutical market: 4,8 bln EUR

3. Poland - general info GDP = 567,400 bn USD (rank 18) Republic of Poland GDP per capita in 2008 = 17,482 USD (rank 50) GDP per capita in 2008 = 17,482 USD (rank 50)

4. POLAND MACROECONOMICS 2009 GDP growth (annual) 3,1% GDP growth (annual) 3,1% Inflation rate 2, 6% Inflation rate 2, 6% Unemployment 12,9% Unemployment 12,9% Salary (mean) 1081,2 USDSalary (mean) 1081,2 USD

5.  Established in January 2005  Established in January 2005 ISPOR POLAND CHAPTER  140 members Polish Society of Pharmacoeconomics (PTFE)

6. WHAT IS BIOLOGICS Biologic- a medicinal product that is synthesized from a living organism or its products Biologic- a medicinal product that is synthesized from a living organism or its products Small molecule drug: a drug synthesized via a chemical process Small molecule drug: a drug synthesized via a chemical process

7. Immune mediated effects are inherent in their activity, but hypersensitivities are rare and mainly due to immunoglobulins (IgE, IgG) BIOLOGICS Structurally similar to autologous proteins, large peptide/proteins Are digested and processed, but not metabolized Parenteral application required

8. BIOLOGICS VACCINES VACCINES BLOOD & BLOOD COMPONENTS BLOOD & BLOOD COMPONENTS ALLERGENICS ALLERGENICS SOMATIC CELLS SOMATIC CELLS GEN THERAPY GEN THERAPY TISSUES TISSUES RECOMBINANT THERAPEUTIC PROTEINS RECOMBINANT THERAPEUTIC PROTEINS

9. DEPLETING CELLS BY ANTIBODIES BIOLOGICALS – tools to affect inflammatory or malignat cells CYTOKINES ANTI - CYTOKINES BLOCKING LIGANDS

10. Prices for biologics have increased more rapidly than prices for small molecule drugs KEY DIFFERENCES between BIOLOGICS and SMALL MOLECULE DRUGS A follow-on biologic cannot be exactly identical to its reference products because of the large size and complexity of the molecules Biologics have specific safety risk involving immunogenicity Biologics tend to be more expensive than small molecule drugs

11. BIOLOGICS IMPACT ON MEDICAL FIELDS RHEUMATOLOGY RHEUMATOLOGY ONCOLOGY ONCOLOGY CARDIOLOGY CARDIOLOGY DERMATOLOGY DERMATOLOGY NEUROLOGY NEUROLOGY PNEUMONOLOGY PNEUMONOLOGY

12. IMS HEALTH : Biotechnology in global pharmacutical market in 2009 (bln USD)

13. IMS HEALTH : Biologics Sales –top three categories in 2009 (blnUSD)

14. Monoclonal antibodies – 80% of SALES

15. Biological agents Subclassification of adverse side effects based on immunopathology & actions of compounds Type  - high cytokine & cytokine release syndrome Type  - high cytokine & cytokine release syndrome Type β – hypersensitivity (immediate & delayed ) Type β – hypersensitivity (immediate & delayed ) Type γ – immune or cytokine imbalance syndromes (e.g autoimmunity, allergic disorders) Type γ – immune or cytokine imbalance syndromes (e.g autoimmunity, allergic disorders) Type δ – cross-reactant Type δ – cross-reactant Type ε – non - immunological side effects Type ε – non - immunological side effects Pichler, Allergy 2006

16.  Few cases of anaphilactic shock even after following doses  30 min to > 24 h after injection  Longer observation required  Suitable equipment of healthcare insitutions required 85 Xolair – anaphilactic shock

17. γ) Cytokine Imbalance Syndromes BIOLOGICS –CIS (type γ) Cytokine Imbalance Syndromes They are not allergic side effects and are clinically characterised by different symptoms which do not correspond to classical allergy Are dependent on the underlying homeostasis/immune balance of the individual patient

18. Biologics – side effects cytokine storm

19. BIOLOGICS –side effects TNF-alfa blockers Allergy (acute infusion SSLR) Allergy (acute infusion SSLR) Autoimmunity (pancytopenia, demyelitating disease Autoimmunity (pancytopenia, demyelitating disease Immunodeficiency (e.g. loss of control of intracellular bacteria- Mycobacteriosis) Immunodeficiency (e.g. loss of control of intracellular bacteria- Mycobacteriosis) Cutaneous (vasculitis) Cutaneous (vasculitis) Malignancy lymphoma Malignancy lymphoma Seizure disorders Seizure disorders Aggravation of heart failure Aggravation of heart failure

20. NHF (National Health Fund) THERAPEUTIC PROGRAMS (n=41) Ca mammae - Trastuzumab Ca mammae - Trastuzumab Chronic mieloblastic leucemia – Imatinib Chronic mieloblastic leucemia – Imatinib GIST – Imatinib or Sunitinib GIST – Imatinib or Sunitinib Multiple sclerosis – Interferon beta Multiple sclerosis – Interferon beta Hepatitis B or C – Interferon alfa Hepatitis B or C – Interferon alfa Kidney carcinoma - Sunitinib Kidney carcinoma - Sunitinib Rheumatoid ar t hritis – Infliximab or Etanerceptum or Adalimumab Rheumatoid ar t hritis – Infliximab or Etanerceptum or Adalimumab

21. NHF (National Health Fund) THERAPEUTIC PROGRAMS QUALIFICATION Application of National Consultant in special field of medicine Application of National Consultant in special field of medicine Submission of the application to the Ministry of Health Submission of the application to the Ministry of Health Recommendation of HTA (AOTM) in cooperation with Consultative Council (CC) commissioned by the Ministry of Health Recommendation of HTA (AOTM) in cooperation with Consultative Council (CC) commissioned by the Ministry of Health

22. AOTM Recommendation Description of medical problem Description of medical problem Description of existing clinical practice Description of existing clinical practice Clinical effectiveness Clinical effectiveness Safety analysis Safety analysis Cost effectiveness Cost effectiveness Budget impact analysis Budget impact analysis Pri c e negotiation s and risk sharing recommendations optionally Pri c e negotiation s and risk sharing recommendations optionally

23. Rheumatoid arthritis ONE YEAR of ANTI- TNF IN POLAND (USD ) No of DOSeS/YEAR POINTS/MGHOSPITALI SATION/one day COST /YEAR TOTAL COST ETANERECEPT 50mg/week 512,10 19 626 ADALIZUMAB 40mg/2 weeks 265,30 20 02020 920 INFLIKSIMAB 200mg/dosis 8 (3+5)2,11224 12 42713 651 INFLIKSIMAB 300mg/dosis 8 (3+5)2,11224 18 64119 865

24. standard Cost-effectiveness analysis of omalizumab v.s. standard therapy in the management of severe asthma Cost –effectiveness – days free of symptoms Martinez-Revelles M.et all., ISPOR 2007, Novartis, Mexico Martinez-Revelles M.et all., ISPOR 2007, Novartis, Mexico USD 250 000 200 000 150 000 100 000 50 000 0 280 300 320 340 360 380 dni Omalizumab

25. XOLAIR What was the price in 2008 ? USA UK Canada Poland 1150,99 USD/amp (150 mg/1.2 ml) 647,58 GBP/amp (180 mg/1.2 ml) 971,62 USD/amp (150 mg/1.2 ml) 633 PLN/amp (150 mg/1,2 ml)

26. Xolair – every 4 weeks > 500 - 600 > 400 - 500 > 300 - 400 300 mg (2 amp.) > 200 - 300 300 mg (2 amp.) > 100 - 200 300 mg (2 amp.) 150 mg (1 amp.) > 30 - 100 > 90 - 150> 70 - 90> 60 - 7030 - 60 Weight (kg) Ig E level (IU/ml)

27. Xolair – every 2 weeks 375 mg (2 1/2 amp.) > 600 - 700 No treatment 375 mg (2 1/2 amp.) 300 mg (2 amp.) > 500 - 600 375 mg (2 1/2 amp.) 300 mg (2 amp.) > 400 - 500 300 mg (2 amp.) 225 mg (1 1/2 amp.) > 300 - 400 300 mg (2 amp.) 225 mg (1 1/2 amp.) > 200 - 300 225 mg (1 1/2 amp.) > 100 - 200 Look at previous slide > 30 - 100 > 90 - 150 > 70 - 90> 60 - 7030 - 60 Weight (kg) IgE level (IU/ml)

28. One year of anti TNF-alfa and anti IgE ( USD mean) v.s. GDP & Salary in Poland (2009)

29. NHF - costs of therapeutic programs in 2010 (PLN )