PROVENGE consists of autologous peripheral blood mononuclear cells, including antigen presenting cells (APCs), that have been activated during a defined culture period with a recombinant human protein, PAP-GM-CSF, consisting of prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator.
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PARAMETER |
DATA |
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Manufacturer |
Dendreon Corporation |
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Transgene |
Autologous peripheral blood mononuclear cells (PBMCs) |
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Indication |
PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer |
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Virus and Serotype |
Baculovirus expression vector |
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Cell Substrate |
Sf21 cell line |
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Manufacturing platform |
Provenge is manufactured from a patient’s own peripheral blood cells obtained via apheresis (APH). The APH is considered a cellular starting material. The manufacturing process involves several concentration and separation steps using proprietary separation solutions and devices to reduce certain cell types. The resulting population is then incubated with the fusion protein PA2024 under specified conditions (temperature and time), to activate the antigen presenting cells. Following incubation with the antigen, the cells are aseptically harvested, washed, suspended in lactated ringers, and packed for delivery to the infusion center. |
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Dose in vial/final container |
50 million autologous CD54+ cells activated with PAPGM-CSF, suspended in 250 mL of Lactated Ringer’s Injection, USP in a sealed, patient-specific infusion bag. |
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Dose/patient |
3 doses at approximately 2-week intervals. |
SUPPORTING CLINICAL TRIALS
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NCT |
TRIAL PHASE |
SUBJECTS ENROLLED |
TITLE |
COUNTRIES |
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NCT00005947 |
3 |
127 |
United States |
|
|
NCT00065442 |
3 |
512 |
United States, Canada |
|
|
NCT00779402 |
3 |
176 |
United States |
|
|
NCT00849290 |
2 |
113 |
Immunotherapy for Men With Objective Disease Progression On Protocol D9902 Part B (NCT00065442) |
United States, Canada |
|
NCT01133704 |
3 |
98 |
|
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04/29/2010 |
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09/06/2013 (withdrawn) |
EMA approval date |
The original BLA for sipuleucel-T for treatment of prostate cancer was submitted in 2006. That application was based on results from Studies D9901 and D9902A. On March 29, 2007, FDA held an advisory committee meeting (Cellular, Tissue and Gene Therapies Advisory Committee, supplemented by members of the Oncology Drugs Advisory Committee and several prostate cancer specialists) to seek advice on the persuasiveness of the sipuleucel-T efficacy and safety results. In addition, several questions regarding product potency, variability, and mechanism of action were discussed.
After complete review of the original BLA submission, the FDA determined that the efficacy result in the original application was not statistically persuasive. Therefore, the FDA issued a complete response letter requiring submission of the results of Study D9902B before licensure.