Lantidra
donislecel
Species
no relevantMonkeyRatMouse
Longest study
none
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Partial / alternative Partly stated
Speciesopen answer page →
Species
No studies with product; literature only (diabetic mice, rats, NHP, pigs)
“No nonclinical studies were conducted with LANTIDRA.”
Why that species
Published diabetic rodent and NHP islet transplant models used to support activity, liver distribution and need for immunosuppression
“The findings of these studies support inclusion of immunosuppression as a critical component for successful islet engraftment and survival following transplant in diabetic animals.”
Surrogate molecule
Yes: literature studies with animal allogeneic/syngeneic islets (no studies with clinical product)
“Pancreatic islets were isolated from C57BL/6 or BALB/C mice (9 weeks old, 20-22 g).”
Study lengthopen answer page →
Longest pivotal study
0 (no in vivo tox study)
“No toxicology studies with LANTIDRA were conducted.”
Pivotal GLP studies
None; publications on intraportal islet allograft safety (e.g., diabetic mouse liver morphology study) cited instead
“The applicant provided publications assessing the overall safety of islet allografts following intraportal transplantation in Module 4 of the BLA.”
Route in tox
Intraportal (hepatic portal vein) transplantation in published models
“were transplanted with 400 allogeneic islets via the portal vein.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted
“No genotoxicity studies with LANTIDRA were conducted.”
Carcinogenicity
Not conducted; literature hepatic tumors in rats with low islet numbers, risk considered low
“Thus, the carcinogenic risk of LANTIDRA in transplanted patients is considered low.”
Reproductive & developmental
Not conducted
“No DART studies with LANTIDRA were conducted.”
Safety pharmacology
Not stated in public reviews
First doseopen answer page →
First-in-human starting dose
No nonclinical basis; target 10,000 EIN/kg from prior Edmonton Protocol clinical experience
“In both UIH-001 & UIH-002 studies a target islet dose of 10,000 EIN/kg was proposed based on the findings of previous experience with Edmonton Protocol for allogeneic islet transplantation.”
NOAEL / key findings
No NOAEL; literature mouse intraportal allografts: emboli, thrombosis, focal liver necrosis without immunosuppression
“These findings were observed on Day 1, progressed to necrotic regions surrounded by multifocal leucocyte infiltrates by Day 3, with progressive mononuclear leukocyte infiltration of the colonized islets (from peri-islet to intra-islet), leading to islet destruction by Days 9-14.”
Risksopen answer page →
Immune & cytokine safety
Allograft rejection without immunosuppression in mice; clinical HLA sensitization (donor-specific antibodies) risk
“These data suggest that an immunosuppression regimen is necessary for islet survival post-transplant and provide overall support for use of the (revised) Edmonton Protocol with intraportal transplantation of LANTIDRA in the target patient population.”
Biodistribution & persistence
Literature pig PET: labeled islets heterogeneously in liver, no extrahepatic accumulation
“The distribution of the 18F-FDG-labeled islet cells in the liver was found to be heterogeneous. No accumulation of radioactivity was detected in non-hepatic tissues.”
Modality-specific risk
Intraportal liver toxicity (thrombosis, necrosis), immunosuppression need, hormonal hepatocarcinogenesis
“This combination of islet number, hyperinsulinism, and hyperglycemia resulted in liver tumors.”