The Unpublished Data

Hunting the Cell Loss Data

*NEW*: "Placebo" patients had 20 billion lymphocytes removed. This is NOT a 'sugar pill'

Both the JNCI paper and this website refer to the numbers and percentages of cells lost from patients in the two arms of the trials. However, these data do not appear anywhere in the published or internal FDA documents and were arduous to derive. This document shows where the key information was sourced, and walks through the steps required to arrive at the final answers. Hunting the Cell Loss Data.pdf

Statistical Analysis of the Age Data

*NEW*: Interaction of placebo intervention with age was more significant than treatment effect

Both the JNCI paper and this website refer to the statistical significance of the problematic age data. The analysis calculates backwards from the medians and confidence intervals (which is less accurate than if the raw data were public), yet the conclusions are so prominent that they cannot be ignored. This document steps through the analysis conducted by a statistician and the conclusions which one might draw with no a priori expectations. Statistical Analysis of the Age Data.pdf

Sources

The “Alternative Explanation” was proposed after considering the balance of evidence offered when considering both published and unpublished data. Published data from the medical literature and company presentations was combined with unpublished data from the following sources:

FDA Provenge Approval Documents – released after approval:

All 160+ documents
http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm213554.htm

2010 Summary Basis for Regulatory Action 
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM213114.pdf

2010 Clinical Review
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214540.pdf

2010 Final CMC Review
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214565.pdf
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214287.pdf

2010 Medical Officer’s Review Memorandum
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214538.pdf

2010 Statistical Review and Evaluation
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214543.pdf

2009 Pre-BLA Meeting Notes
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214574.pdf

2007 Clinical Team Leader BLA Review Memo
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214562.pdf

2007 Medical Review
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214560.pdf

2007 Pharmacology & Toxicology Review
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM227998.pdf

2007 Statistical Review
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM214567.pdf

2007 Teleconference Memmorandum
http://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM213990.pdf

2007 FDA Advisory Committee Meeting - available since 2007:

Briefing Documents (by Dendreon and FDA)
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4291B1-00-index.htm

Presentations (by Dendreon and FDA)
http://www.fda.gov/ohrms/dockets/ac/07/slides/2007-4291S1-00-index.htm

Transcript
http://www.fda.gov/ohrms/dockets/ac/07/transcripts/2007-4291T1.pdf

2010 AHRQ Technology Assessment for Medicare

February 2010 Technology Assessment
https://www.cms.gov/determinationprocess/downloads/id77TA.pdf

Dendreon at Medical Conferences - Posters and Presentations

June 2010 - ASCO Presentation - Correlation between Cumulative Product Parameters and Overall Survival
ASCO_2010_Presentation_-_Correlation_Between_Product_Parameters_and_Overall_Survival_in_Provenge_Trials_-_Stewart.pdf

June 2010 - ASCO Poster - Correlation between Cumulative Product Parameters and Overall Survival
ASCO_2010_Poster_-_Correlation_Between_Product_Parameters_and_Overall_Survival_in_Provenge_Trials_-_Stewart.pdf

June 2011 - ASCO Poster - Post-Progression Treatment with APC8015F may have Prolonged Survival in the Control Arm of Provenge Trials
ASCO_2011_Poster_-_Prolonged-Survival-in-Control-Arm-Sip-T-Gomella.pdf
ASCO_2011_Poster_-_Prolonged-Survival-in-Control-Arm-Sip-T-Gomella_PHOTO.pdf

Dendreon Patents

US 6,210,662 - 2001 Patent on PAP-GMCSF Antigen
http://www.wikipatents.com/US-Patent-6210662/immunostimulatory-composition

US 7,413,869 - 2008 Patent on 'Method for determining potency of APC-based cell vaccines
http://www.wikipatents.com/US-Patent-7413869/method-for-determining-potency-of-antigenic-presenting-cell-based