Lyfgenia
lovotibeglogene autotemcel
Species
Mouse
Longest study
26 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 (beta-thalassemic and wild-type C57BL/6 transplant models; immunodeficient mice for human cells)
“The following toxicology studies were conducted to evaluate the safety of human HSCs or mBMCs transduced with BB305 LVV following administration in mice.”
Why that species
Beta-thalassemic (Hbbth1/th1) mouse disease model allowed pharmacology and toxicity assessment of transduced syngeneic marrow
“To evaluate the pharmacologic and toxicologic effects of mBMCs transduced with BB305 LVV or mBMCs transduced with HPV569 LVV following IV administration in β-thalassemic mice.”
Surrogate molecule
Yes: murine bone marrow cells transduced with clinical BB305 vector (homologous cell product); human CD34+ in immunodeficient mice
“Test Articles • mBMCs transduced with BB305 LVV (Lot No. • mBMCs transduced with HPV569 LVV (Lot No. Control Article mBMCs; mock-transduced”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“Scheduled Sacrifice Time Points 6 months post-transplant”
Pivotal GLP studies
Non-GLP single-dose IV studies: primary transplant in beta-thal mice (4 months) and secondary transplant in C57BL/6 mice (6 months)
“In vivo studies were also conducted to assess the activity and safety of mBMCs transduced with BB305 following primary and secondary transplantation in β-thalassemic and wild-type C57BL/6 mice.”
Route in tox
Intravenous (after irradiation or busulfan myeloablation)
“Route of Administration IV injection”
Skipped studiesopen answer page →
Genotoxicity
Insertional mutagenesis assessed: in vitro immortalization (IVIM) assay and integration site analyses; low risk
“Per the applicant, based on these data, the risk of insertional mutagenesis following BB305 transduction is low.”
Carcinogenicity
Not conducted (acceptable based on product type)
“No traditional carcinogenicity studies were conducted with lovo-cel which is acceptable based on the product type.”
Reproductive & developmental
Not conducted (no reproductive tissue findings in mouse studies; busulfan risk addressed in label)
“Per the applicant, developmental and reproductive toxicology studies were not conducted because there were no adverse findings in the male and female reproductive tissues of mice administered mBMCs transduced with BB305 LVV”
Safety pharmacology
Not conducted
“No safety pharmacology studies with lovo-cel were conducted.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
Applicant designated single tested dose (11x10^6 cells/kg) NOAEL; no test article-related deaths or adverse findings through 6 months; lymphomas background
“In the secondary transplantation study, no deaths or adverse findings attributed to the BB305 LVV-transduced cells occurred through 6 months post-transplantation of 6×106 cells/mouse.”
Risksopen answer page →
Immune & cytokine safety
Not stated in public reviews
Biodistribution & persistence
No traditional PK; cell distribution assessed by VCN in bone marrow and peripheral blood
“Cell distribution was assessed by the applicant in the target tissues, BM, and peripheral blood, by VCN measurements.”
Modality-specific risk
Insertional oncogenesis from LVV integration; T-cell lymphomas in serial transplant mice judged incidental (low VCN in tumors)
“A mean VCN of <1 was detected in the analyzed thymus and BM tissues, suggesting that the tumors found in the animals were not linked to high vector copy numbers.”