Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Talvey: genotox, carcinogenicity and repro: done or skipped?
talquetamab · GPRC5D x CD3
Genotoxicity
Not conducted (ICH S6; biotechnology-derived product)
“Genotoxicity studies routinely conducted for pharmaceuticals have not been conducted and are not applicable to biotechnology-derived pharmaceuticals such as talquetamab per ICH S6.”
Carcinogenicity
Not conducted (ICH S9; advanced cancer)
“As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”
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 (weight-of-evidence assessment; ADA limits exposure, no relevant species); reproductive organs examined in repeat-dose study
“We agree with the Applicant’s WOE-based approach for the assessment of reproductive and developmental toxicity.”
Safety pharmacology
Incorporated into 1-month GLP monkey study with tool molecule (CV, respiratory, CNS); no effects
“However, cardiovascular, respiratory, and observational CNS safety pharmacology endpoints were incorporated into the 1-month GLP repeat dose toxicity study conducted with the tool molecule in cynomolgus monkeys”
Genotox: Ames
Not conducted (ICH S6)
“Genotoxicity studies routinely conducted for pharmaceuticals have not been conducted and are not applicable to biotechnology-derived pharmaceuticals such as talquetamab per ICH S6.”
Genotox: in vitro mammalian
Not conducted (ICH S6)
“Genotoxicity studies routinely conducted for pharmaceuticals have not been conducted and are not applicable to biotechnology-derived pharmaceuticals such as talquetamab per ICH S6.”
Genotox: in vivo
Not conducted (ICH S6)
“Genotoxicity studies routinely conducted for pharmaceuticals have not been conducted and are not applicable to biotechnology-derived pharmaceuticals such as talquetamab per ICH S6.”
Carcinogenicity model
Not conducted (ICH S9, advanced cancer)
“Carcinogenicity studies were not conducted with talquetamab. As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”
Carcinogenicity timing
Not required (FDA agrees not warranted)
“We agree that carcinogenicity studies are not warranted to support the approval of BLA 761342.”
hERG / QT
No hERG assay; tool molecule up to 30 mg/kg weekly had no effect on ECG, blood pressure, heart rate in monkeys
“The tool molecule (JNJ-64024701) at weekly IV doses up to 30 mg/kg had no effect on cardiovascular (electrocardiograms, blood pressure, heart rate), respiratory (respiration rate), or CNS (clinical observations and body temperature) parameters evaluated up to Week 4”
Same question, other multispecifics
Blincyto
blinatumomab · CD19 x CD3Not conducted (ICH S6(R1); protein of natural amino acids)
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)
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)