1. Jennifer Dao Phan Gaëlle Datchoua Emmanuel Gomez UEI2 Scientific communication Workshop February 11 & 12, 2010
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3. Product: Sipuleucel-T (Provenge®) Laboratory: Dendreon Indication: asymptomatic metastatic Androgen Independent Prostate Cancer Agent: autologous dendritic cells Launch on market: expected for mid-2010
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5. Summary for Prostate Cancer epidemiology Jemal et al. CA Cancer J Clin. 2009;225-249. Commun Oncol 2007;4:447–452 15% Metastatic disease Prostate cancer Initial diagnosis 85 % localized early disease 60-70% Localized disease 30-40% Relapse disease ~ 18-36 months
6. Diagnosis of advanced prostate cancer Gleason’s score PSA doubling time Residual testosteronemia > 50 ng/mL Digital Rectal Examination+Biopsy Blood test Research of metastases
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9. Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA . 2005;294:433-439. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA . 1999;281:1591-1597. Gleason’s Score + PSA DT = predictive for PCa outcome
10. Asymptomatic metastatic PCa : no approved therapies in European guidelines A gap for brand new treatment strategies? Asymptomatic metastatic PCa: a medical unmet need Adaptated from : Nature Reviews Cancer 2 , 389-396 (May 2002) Progrès en Urologie (2008), Suppl. 7, S343–S348 Commun Oncol 2007;4:447–452
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17. Antigen Presentation to T Cells (BARAS, LICHTMAN, Cellular and Molecular Immunology, Saunders ed., 5e ed., 2003) Secondary lymphoid organs Peripheral tissues Th1/Th2 pathway Macrophage/ B cell activation Cytotoxic effect against targeted cells
18. How to break the tolerance CD 4 – CD8 LFA - 3 ICAM – 1(=CD54) CD 40 B7 (CD80 and CD86) LFA - 1 CD 2 CD 40 L -S–S - CD 28 T-Cell Antigen Presenting Cells MHC peptide Complexe, I or II -S– S - TCR - CD 3 Peptide
31. Consistency Across Phase 3 Studies *Unadjusted Cox model & log rank **Cox model adjusted for PSA and LDH
32. Keep an eye on … Group Sipuleucel-T n / N (%) Placebo n / N (%) Odds Ratio (95% CI) p-value All Subjects All CVA’s 18 /461 (3.9%) 6/231 (2.6%) 1.52 (0.596, 3.892) 0.510 Deaths attributed to CVAs 7 / 461 (1.5%) 2 / 231 (0.9%) 1.76 (0.364, 8.566) 0.725 AIPC (Proposed Indication) All CVA’s 17 / 345 (4.9%) 3 / 172 (1.7%) 2.92 (0.84, 10) 0.092 Deaths attributed to CVAs 7 / 345 (2.0%) 2 / 172 (1.2%) 1.76 (0.36, 8.6) 0.724 ADPC (P-11) All CVA’s 1 / 116 (0.9%) 3 / 59 (5.1%) 0.16 (0.016, 1.596) 0.112 Deaths attributed to CVAs 0 0 --- ---
33. PROTECT (P11): PROVENGE Treatment and Early Cancer Treatment. Ongoing Phase 3 trial with enrollment completed
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38. Sipuleucel-T (Provenge ® ) production and delivery PROVENGE® (sipuleucel-T) Cellular, Tissue, and Gene Therapies Advisory Committee Meeting March 29, 2007 The Mattson Jack Group, Cancer Metric Database 2009 COMPLETE COURSE OF THERAPY: 3 CYCLES 100 000 patients in USA with metastatic AIPC in 2010 100 000 X 3 = 300 000 doses to prepare and to deliver on time How will Dendreon make it? Day 1 Leukapheresis Apheresis Center Day 2-3 Manufacturing Dendreon’s facility Day 3-4 Infusion Doctor’s Office
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41. Exemple of a workstation to manufacture Provenge
42. Exemple of a workstation to manufacture Provenge
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