Tudriqev
vusolimogene oderparepvec
Sources:FDA summary basis for approval ↗
Species
RatMouse
Longest study
26 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Tumor-bearing immunocompetent mice (TUDRIQEV, mRP1) and healthy rats (murine surrogate mRP1)
“Toxicology studies evaluating TUDRIQEV and mRP1 were conducted in tumor-bearing immunocompetent mice and healthy rats, respectively.”
Why that species
Not stated in public reviews
Surrogate molecule
Yes: mRP1, identical to clinical product except murine GM-CSF replaces human GM-CSF
“a murine surrogate product, mRP1 (identical to TUDRIQEV, except that human GM-CSF is replaced by murine GM-CSF)”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“No adverse findings were observed up to 6 months following repeat administration of mRP1 (16 total doses; up to 1x106 PFU/animal/injection) in healthy rats.”
Pivotal GLP studies
Single and repeat-dose mRP1 studies in healthy rats (16 doses, 6-month follow-up); repeat IT TUDRIQEV in tumor-bearing mice (5 doses)
“Toxicology studies evaluating TUDRIQEV and mRP1 were conducted in tumor-bearing immunocompetent mice and healthy rats, respectively.”
Route in tox
Intratumoral (mice) and intravenous/other routes (rats); IV in embryofetal study
“Repeat IT administration of TUDRIQEV batches manufactured at two different sites”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (not warranted based on product characteristics and safety profile)
“Studies to evaluate the safety pharmacology, genotoxicity, and carcinogenicity of TUDRIQEV were not conducted.”
Carcinogenicity
Not conducted (not warranted)
“Studies to evaluate the safety pharmacology, genotoxicity, and carcinogenicity of TUDRIQEV were not conducted.”
Reproductive & developmental
Embryofetal study in pregnant rats (mRP1 IV, GD 4-16): no malformations or growth effects; minimal placental transfer
“no embryofetal structural abnormalities or adverse effects on embryofetal growth were observed following repeat IV mRP1 administration.”
Safety pharmacology
Not conducted (not warranted)
“Studies to evaluate the safety pharmacology, genotoxicity, and carcinogenicity of TUDRIQEV were not conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
NOAEL = highest dose tested of mRP1 in rats, 1x10^7 PFU/animal/injection; no adverse findings
“was 1x107 plaque-forming units (PFU)/animal/injection, which was the determined no-observed-adverse-effect level for all studies.”
Risksopen answer page →
Immune & cytokine safety
No test-article-related adverse findings in tumor-bearing mice; RNAseq showed immune infiltration/inflammation genes in injected tumors
“showed increased expression of genes associated with immune cell infiltration and inflammation in injected tumors compared to non-injected tumors”
Biodistribution & persistence
Viral genomes mainly at injection site; mRP1 DNA in blood, organs, ovaries, neural tissue in rats to Day 71; no latency/reactivation at 6 months
“viral genomes were predominantly present at the injection sites (i.e., tumor), irrespective of the route of administration.”
Modality-specific risk
HSV-1 latency/reactivation, neural tissue distribution and viral shedding; minimal risk seen at 6 months
“indicating minimal risk of latency and reactivation of mRP1.”