Avanserte terapier (kommer snart til et sykehus nær deg)

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1 Avanserte terapier (kommer snart til et sykehus nær deg) Seminar for legemiddelkomiteer 4. juni 2014 Rune Kjeken, PhD

2 Advanced Therapy Medicinal Products (ATMP) Gene therapy medicinal products Somatic cell therapy medicinal products Tissue engineering products Genetically modified cells Nat Biotechnol 2005, 23(7)

3 ATMPs Defined as medicinal products Gene therapy medicinal products Somatic cell therapy medicinal products Tissue engineering products Genetically modified cells Nat Biotechnol 2005, 23(7) Central marketing authorisation is mandatory for ATMPs

4 Committee for Advanced Therapies (CAT) CAT covers the scientific areas relevant to advanced therapies, including: - medical devices - tissue engineering - gene therapy - cell therapy - biotechnology - surgery - pharmacovigilance - risk management - ethics

5 ATMP i kliniske studier i EU EudraCT data Antall ATMPer: Genterapi: 67 Celleterapi og vevsterapi: 240 Fordelt på faser: Phase I = 106 Phase II =165 Phase III =48

6 ATMP godkjente eller i kjømda EudraCT data 4 godkjent hittil (4 avslått) 2 vevsterapier 1 celleterapi 1 genterapi Kommer (kanskje) innen celleterapier 2-3 vevsterapier 2-3 genterapier

7 ChondroCelect approved July 2009 Autologus chondrocytes in suspension 1 st generation treatment of cartilage defect in the knee

8 Maci approved July 2013 Autologus chondrocytes in suspension 3 rd generation treatment of cartilage defect in the knee

9 Vevsterapi Hva kommer? Flere condrocyttpreparater Horninner basert på stamceller En mengde ulike produkter basert på mesenkymale stamceller fra beinmarg eller fettvev Bioprinting

10 Glybera - godkjent av EMA 2012 Genterapi for Lipoprotein lipase (LPL) mangel Sykdom: Mangler enzymet for å metabolisere fettstoffer i blodet; svært sjelden; fettfattig kosthold; pankreatitter Genet for LPL pakkes inn i et virus (AAV1) IM injection Glybera Reduction Chylomicrons (CM) CM 3H activity (%ID/100 ml) wk-2 wk+14 wk+52 p = 0.18 p = Gis vha ca 50 intramuskulære injeksjoner. time after test meal (hrs) Improved CM handling one year after Glybera in first 3 subjects

11 Genterapi-produkter Hva kommer? Klassisk Genterapi mot sjeldne arvelige sykdommer f.eks: Cystisk fibrose Blødersykdom Muskel dystrofi Kronisk granulomatøs sykdom (CGD) osv Genterapi for massene Genterapi mot kreft Genterapi mot HIV Genterapi mot Influensa Og om bioteknologiloven endres: Genterapi på foster?

12 PROVENGE approved by EMA June 2013 (FDA April 2010) Indication: Treatment of metastatic castrate resistant prostate cancer Immune response directed against PAP (prostatic acid phosphatase) protein

13 PROVENGE

14 Cellebaserte produkter mot kreft Hva kommer? Immunterapi mot kreft Genmodifiserte T-celler med CAR (Chimeric Antigen Reseptor)

15 Targeting Cancer with autologous CAR T cells T cells T cell stimulation/ amplification Cytotoxic lymphodepleting conditioning Traditional dose: x 10 7 T cells/kg Patient Patient CAR Transduction 2-3 weeks

16 Targeting Cancer with autologous CAR T cells 2-3 weeks

17 Targeting CD19+ leukemia with autologous CAR T cells

18 Targeting CD19+ leukemia with autologous CAR T cells Chronic Lymphocytic Leukemia (CLL) Acute Lymphoblastic Leukemia (ALL) Almost 100 patients treated to date Very late stage disease Disease resistant to chemotherapy Mutations with bad prognosis pounds of tumor/patient

19 Targeting CD19+ leukemia with autologous CAR T cells Complete remission rates above 50% No age dependent efficacy (CLL) No dose response relationship 1000 fold expansion of CAR T cells in vivo Each infused CAR T cell killed more that 1000 tumor cells

20 Targeting CD19+ leukemia with autologous CAR T cells Tumor lysis /Cytokine release syndrome B Cell aplasia Long term safety? Limitations due to patient and need for autologous cells

21 2 nd generation: allogenic CAR T cells? Allogeneic cells (bone marrow) EliminatingTCR : no GvHD suicide epitope to trigger cell destruction if needed.

22 Targeting cancer with autologous CAR T cells CAR T cells for solid tumors? Robotic T cell culture: scale up Learn how to manage CAR toxicities FDA/EMA approval for CLL, ALL

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24 Genterapi mot HIV

25 Oppsummering: Advanced therapy medicinal products (ATMPs) Definert som medisinske produkter Kan behandle en rekke sykdommer og skader Mange behandlingsmuligheter allerede i dag Mange utfordringer, bl. a. relatert til produktet selv Må godkjennes før bruk Eksperter og spesialutstyr på sykehus er ofte nødvendig

26 Takk for oppmerksomheten! Rune Kjeken Tlf: