Waskyra
etuvetidigene autotemcel
Species
Mouse
Longest study
64 wk
Genotox
Partial / alternative Partial / alternative
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Mouse only: WAS knockout (C57BL/6 and SV129) mice with murine surrogate cells; Rag2-/-IL2rg-/- mice for human-cell fate
“Two different WAS disease models were used to evaluate in vivo safety of transduced HSPCs: a WAS knockout (WKO) mouse on a C57BL/6 background”
Why that species
Autologous human cells cannot be used in animals; murine Lin- HSPCs functionally equivalent to human CD34+; Rag2-/-IL2rg-/- avoids immunogenicity
“The impossibility of using autologous human cells in animal models limits the scope of possible nonclinical studies.”
Surrogate molecule
Yes: mouse Lin- HSPCs transduced with w1.6W or clinical w1.6W_mut6 vector as surrogate test article
“In both models, the test article was comprised of a mouse surrogate test article”
Study lengthopen answer page →
Longest pivotal study
64 weeks
“Overall, these studies demonstrated no increased tumorigenic potential over a period of up to 16 months when WAS LVV-transduced HSPCs were transplanted into WAS deficient mice.”
Pivotal GLP studies
No standalone GLP pivotal tox study; two non-pivotal WKO mouse studies (sublethal/lethal irradiation) plus serial transplant, 12-16 months
“No standalone, GLP in vivo pivotal toxicology study has been performed.”
Route in tox
Intravenous
“injected intravenously with Telethon003 (0.3 x 106 cells per animal)”
Skipped studiesopen answer page →
Genotoxicity
Conventional mutagenicity not conducted; IVIM assay, vector insertion site analysis and VITA performed, no genotoxic potential
“No mutagenicity, carcinogenicity and reproductive and developmental toxicity studies have been performed with WASKYRA”
Carcinogenicity
Not conducted (not suited to product); tumorigenicity assessed in mouse toxicity and serial transplant studies up to 16 months
“While, standard carcinogenicity studies are usually not required due to the nature of the advanced medicinal product”
Reproductive & developmental
Not conducted; no vector in testes, no treatment-related effect on reproductive organs in mouse surrogate study
“No carcinogenicity, developmental and reproductive toxicology (DART) studies, and safety pharmacology studies were conducted for WASKYRA.”
Safety pharmacology
Not conducted (WASP expressed under WAS promoter, accidental expression in heart unlikely)
“No standalone safety pharmacology studies have been conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; no increased mortality, tumorigenicity or toxicity related to transduced HSPCs; lymphomas were of host origin
“results do not reveal any increased mortality, tumorigenicity, or other forms of toxicity related to the transduction of mouse SV129 WKO Lin- HSPCs with w1.6W LVV.”
Risksopen answer page →
Immune & cytokine safety
No dedicated immunotox studies; no anti-WASP antibodies in 27 treated patients
“No anti-WASP antibodies have been detected in any of the 27 participants treated with WASKYRA”
Biodistribution & persistence
Distribution limited to hematopoietic tissues; no vector in brain or testes, no bystander transduction or germline transmission
“No human or LVV sequences were detected in non-hematopoietic tissues (brain and testes)”
Modality-specific risk
Insertional mutagenesis/oncogenesis of integrating LVV; mitigated by SIN design and low VCN; 15-year follow-up required
“However, the risk of insertional mutagenicity with the integrative viral vector is an established feature, albeit mitigated in that case by the SIN virus and low VCN.”