Blincyto
blinatumomab · CD19 x CD3Not conducted (ICH S6(R1); protein of natural amino acids)
Bizengri: genotox, carcinogenicity and repro: done or skipped?
zenocutuzumab · HER2 x HER3
Genotoxicity
Not conducted (ICH S6(R1))
“Standard genotoxicity studies are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) guideline.”
Carcinogenicity
Not conducted (ICH S6(R1), ICH S9)
“Carcinogenicity studies have not been performed with MCLA-128 as they are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) and ICH S9 guidelines.”
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
Not conducted; literature weight-of-evidence (HER2/HER3 essential for embryo-fetal development); boxed warning
“The Applicant did not conduct reproductive or embryo-fetal developmental toxicology studies with zenocutuzumab.”
Safety pharmacology
Incorporated into repeat-dose monkey studies (ECG, BP, respiration, temperature, CNS); no effects
“Stand-alone safety pharmacology studies were not conducted. Safety pharmacology was evaluated as part of the general toxicology studies performed with MCLA-128.”
Genotox: Ames
Not conducted (ICH S6)
“Standard genotoxicity studies are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) guideline.”
Genotox: in vitro mammalian
Not conducted (ICH S6)
“Standard genotoxicity studies are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) guideline.”
Genotox: in vivo
Not conducted (ICH S6)
“Standard genotoxicity studies are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) guideline.”
Carcinogenicity model
Not conducted (ICH S6(R1) and ICH S9)
“Carcinogenicity studies have not been performed with MCLA-128 as they are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) and ICH S9 guidelines.”
Carcinogenicity timing
Not required; FDA agreed carcinogenicity studies not warranted
“FDA agrees that carcinogenicity studies are not warranted to support this BLA submission.”
hERG / QT
No hERG assay; no ECG, blood pressure or respiratory effects in monkey repeat-dose studies up to 101 mg/kg/week
“No effect was observed on ECG, blood pressure, respiration rate, body temperature or CNS safety pharmacology parameters evaluated as part of the general toxicology studies performed in cynomolgus monkeys with MCLA-128 up to 101 mg/kg/week”
Same question, other multispecifics
Columvi
glofitamab · CD20 x CD3Not conducted (ICH S6(R1))
Elrexfio
elranatamab · BCMA x CD3Not conducted (ICH S6(R1))
Epkinly
epcoritamab · CD20 x CD3Not conducted (ICH S6(R1), ICH S9)
Hemlibra
emicizumab · FIXa x FXNot conducted (ICH S6)
Imdelltra
tarlatamab · DLL3 x CD3Not conducted (ICH S6(R1))
Kimmtrak
tebentafusp · CD3 x gp100 (TCR fusion)Not conducted (fusion protein; ICH S6/S9)
Korjuny
catumaxomab · EpCAM x CD3Not conducted (ICH S6(R1))
Lunsumio
mosunetuzumab · CD20 x CD3Not conducted (ICH S6(R1))
Lynozyfic
linvoseltamab · BCMA x CD3Not conducted (antibody not expected to interact with DNA)
Ordspono
odronextamab · CD20 x CD3Not conducted (antibody not expected to interact with DNA)
Removab
catumaxomab · EpCAM x CD3Not conducted (not submitted; biologic, no relevant model)
Rybrevant
amivantamab · EGFR x METNot conducted (not appropriate for antibodies)
Talvey
talquetamab · GPRC5D x CD3Not conducted (ICH S6; biotechnology-derived product)
Tecvayli
teclistamab · BCMA x CD3Not conducted (ICH S6(R1))
Vabysmo
faricimab · VEGF-A x Ang-2Not conducted (ICH S6(R1))
Ziihera
zanidatamab · HER2 x HER2 (biparatopic)Not conducted (ICH S6(R1), ICH S9)