Blincyto
blinatumomab · CD19 x CD3Chimpanzee exposure (Cmax 0.9-1.36 ng/mL) higher than human Css at 9 and 28 µg/day; no NOAEL or multiple stated
Elrexfio: what safety margin did regulators accept?
elranatamab · BCMA x CD3
Safety margin at NOAEL
Monkey NOAEL/LOEL 0.3 mg/kg exposure well below human exposure (0.1x or 0.2x)
“At the NOAEL/LOEL of 0.3 mg/kg, exposure in cynomolgus was well below the human exposure (0.1x or 0.2x).”
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”
Same question, other bispecifics
Columvi
glofitamab · CD20 x CD3Monkey exposure below clinical: AUC multiples 0.03-0.28 in studies without obinutuzumab pretreatment
Epkinly
epcoritamab · CD20 x CD3Monkey SC NOAEL 10 mg/kg: 5x clinical steady-state AUC; IV 1 mg/kg exposure equal to clinical AUC
Hemlibra
emicizumab · FIXa x FXMonkey NOAEL (30 mg/kg, 26-week) ~11x human AUC at 3 mg/kg QW
Korjuny
catumaxomab · EpCAM x CD3No margin: surrogate BiLu mouse NOAEL (0.2-3.0 µg/kg) equivalent to the clinical catumaxomab dose (1.43 µg/kg)
Lunsumio
mosunetuzumab · CD20 x CD3No NOAEL; CRS and infections in monkeys at exposures 0.008-1.84x human AUC
Rybrevant
amivantamab · EGFR x METMonkey AUC at 120 mg/kg 5x human AUC at the 1050 mg clinical dose
Tecvayli
teclistamab · BCMA x CD3Monkey NOEL 30 mg/kg IV weekly: 22x AUCtau, 48x Cmax vs human 1.5 mg/kg SC weekly
Vabysmo
faricimab · VEGF-A x Ang-2Ocular NOAEL 0.5 mg/eye (6-month monkey): exposure margin only around 1x human
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Monkey NOAEL 150 mg/kg: exposure ~10-fold above clinically relevant exposure
Bizengri
zenocutuzumab · HER2 x HER3Not stated in public reviews
Imdelltra
tarlatamab · DLL3 x CD3Not stated in public reviews
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Not stated in public reviews
Lynozyfic
linvoseltamab · BCMA x CD3Not stated in public reviews
Ordspono
odronextamab · CD20 x CD3Not stated in public reviews
Removab
catumaxomab · EpCAM x CD3Not stated in public reviews
Talvey
talquetamab · GPRC5D x CD3Not stated in public reviews