Elrexfio
elranatamab
Species
Monkey
Longest study
13 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
Cynomolgus monkey only
“Cynomolgus monkey was identified as the only relevant nonclinical toxicology species based on elranatamab binding affinities for BCMA and CD3.”
Why that species
Comparable binding to cyno and human BCMA and CD3; comparable BCMA+ cell frequency/phenotype
“Selection of cynomolgus as relevant species appears adequate, based on comparable binding affinity of elranatamab to cynomolgus and human BCMA and CD3, and a comparable frequency and phenotype of cynomolgus and human BCMA+ cells.”
Surrogate molecule
No surrogate; clinical molecule tested in monkey
“General toxicology studies were conducted in cynomolgus monkeys, a pharmacologically relevant species to assess the toxicity of elranatamab.”
Study lengthopen answer page →
Longest pivotal study
13 weeks
“In the 3-month repeat-dose SC toxicity study, elranatamab doses of 0.3, 3, and 6 mg/kg/week (total of 14 doses) showed adverse clinical signs that correlated with decreased body weight and food consumption and contributed to mortality.”
Pivotal GLP studies
GLP cynomolgus: 1-month IV (0.01-0.3 mg/kg/wk), 1-month SC (0.3 mg/kg/wk), 3-month SC (0.3, 3, 6 mg/kg/wk); no recovery
“Recovery was not assessed in any of the general toxicology studies.”
Route in tox
IV and SC (SC is clinical route, used for longest study)
“Intravenous administration was originally assessed before subcutaneous administration was chosen as the clinical route.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genotoxicity studies with elranatamab have not been conducted since they are generally not required for protein-based biotherapeutics per ICH S6(R1).”
Carcinogenicity
Not conducted (ICH S9 / S6(R1))
“Carcinogenicity studies with elranatamab have not been conducted since they are generally not required for advanced cancer and protein-based biotherapeutics per ICH S9 and ICH S6(R1), respectively.”
Reproductive & developmental
Not conducted (weight-of-evidence); reproductive organs assessed in 3-month monkey study, no effects
“Embryofetal developmental toxicity was evaluated using a weight of evidence (WOE) risk assessment”
Safety pharmacology
Incorporated into repeat-dose monkey studies (ECG, heart rate; respiratory/CNS by clinical observation)
“No safety pharmacology studies were conducted. Safety pharmacology was evaluated as part of the general toxicology studies performed with elranatamab.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL in 3-month SC study (immunosuppression, infections, moribundity at all doses); NOAEL 0.3 mg/kg/wk in 1-month studies
“Immunosuppression led to secondary infections and moribund euthanasia at all doses; no NOAEL was identified; dose-dependence was evident by incidence and timing”
Risksopen answer page →
Immune & cytokine safety
Transient cytokine increases mainly after first dose; B-cell/plasma cell depletion; ADA incidence up to 67% at low dose
“Increased cytokine levels were considered transient since they were mainly observed after the first dose but not after subsequent doses.”
Biodistribution & persistence
No tissue distribution studies; Vss ~0.1 L/kg in monkey, IgG-like limited distribution
“Protein binding and tissue distribution studies were not conducted for elranatamab in nonclinical species.”
Modality-specific risk
CRS from T-cell activation and immunosuppression/infection from BCMA+ B/plasma cell depletion
“The mode of action of elranatamab is associated with T cell activation and induction of cytokine release. Cytokine release syndrome is an identified risk for elranatamab and adequately addressed in the SmPC and the RMP.”