Provenge
sipuleucel-T
Species
no relevantRatMouse
Longest study
6 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No conventional tox species; rat and mouse proof-of-concept studies with rodent surrogate products
“The immunogenicity and anti-tumour properties of these surrogate products were evaluated in rats and mice.”
Why that species
Autologous human product cannot be tested in animals; species-specific rodent equivalents used (rat/mouse PAP and GM-CSF)
“Animal models using species-specific variations of the human cell therapy product have been used.”
Surrogate molecule
Yes: rat APCs loaded with rPAP-rGM-CSF or hPAP-mGM-CSF fusion proteins; mouse hPAP-hGM-CSF loaded APCs
“The equivalent of sipuleucel-T has been prepared from rat APCs loaded with PAP•GM-CSF fusion proteins”
Study lengthopen answer page →
Longest pivotal study
6 weeks
“On day 42, 4 rats from the control (unimmunised)”
Pivotal GLP studies
None; non-GLP proof-of-concept rat prostatitis and mouse tumor-challenge studies only (rat observation to day 42)
“All pharmacological experiments were proof of concept studies that were non-GLP compliant.”
Route in tox
Intravenous (rat cell infusions); intraperitoneal in mice
“Copenhagen male rats, 10 weeks old, were immunised with three separate intravenous (IV) infusions”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (autologous nature of product)
“Toxicology studies, as described in the International Conference on Harmonization (ICH) Safety (‘S’) guidelines”
Carcinogenicity
Not conducted (autologous nature of product)
“No genotoxicity, reproductive toxicity, mutagenicity and carcinogenicity studies were provided”
Reproductive & developmental
Not conducted
“No genotoxicity, reproductive toxicity, mutagenicity and carcinogenicity studies were provided”
Safety pharmacology
Not conducted as ICH battery; safety observations collected in pharmacodynamic rat and mouse studies
“The general battery of safety pharmacology studies as outlined in the International Conference of Harmonization (ICH) guidelines were not submitted by the applicant.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; cell dose not limited by toxicity; highest feasible dose used in animal studies; no obvious adverse effects in mice
“It was agreed that the cell dose is apparently not limited by toxicity.”
Risksopen answer page →
Immune & cytokine safety
Autoimmune prostatitis induced in rats (mild to moderate); non-prostate PAP-expressing tissues not fully examined; no robust data on autoimmunity risk
“Mild to severe interstitial inflammation was observed in Groups 4-6 rats.”
Biodistribution & persistence
No conventional ADME/biodistribution studies submitted
“No conventional ADME studies were submitted by the applicant”
Modality-specific risk
Autoimmunity against PAP-expressing tissues (prostatitis, non-prostatic tissues); tolerance breaking by design
“The likelihood of auto-immune reactions in non-prostatic tissues expressing PAP cannot be excluded in the clinical setting”