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.”
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”
Same question, other bispecifics
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)