Bizengri
zenocutuzumab · HER2 x HER3Not conducted (ICH S6(R1))
Hemlibra: genotox, carcinogenicity and repro: done or skipped?
emicizumab · FIXa x FX
Genotoxicity
Not conducted (ICH S6)
“Genotoxicity studies were not conducted as these types of studies are not applicable to biotechnology-derived pharmaceuticals (per ICH S6).”
Carcinogenicity
Not conducted (no pharmacologically relevant rodent; waived with ECAC concurrence)
“Carcinogenicity studies were not conducted due to lack of a pharmacologically relevant rodent species.”
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 (99% of patients male); no reproductive organ effects in 26-week monkey study
“Animal reproductive and developmental toxicology studies were not conducted with emicizumab as hemophilia A is inherited in an X-linked recessive manner.”
Safety pharmacology
Incorporated into repeat-dose monkey studies (ICH S6(R1)); no CNS, respiratory or CV effects
“Safety assessment of vital organs was incorporated in the toxicology studies in monkeys.”
Genotox: Ames
Not conducted (ICH S6)
“Genotoxicity studies were not conducted as these types of studies are not applicable to biotechnology-derived pharmaceuticals (per ICH S6).”
Genotox: in vitro mammalian
Not conducted (ICH S6)
“Genotoxicity studies were not conducted as these types of studies are not applicable to biotechnology-derived pharmaceuticals (per ICH S6).”
Genotox: in vivo
Not conducted (ICH S6)
“Genotoxicity studies were not conducted as these types of studies are not applicable to biotechnology-derived pharmaceuticals (per ICH S6).”
Carcinogenicity model
Not conducted (not active in mice or rats; restoring hemostasis not expected to increase tumorigenesis)
“Carcinogenicity studies have not been conducted with emicizumab because the product is not active in mice or rats; restoring hemostasis is not expected to increase the potential for tumorigenesis.”
Carcinogenicity timing
Not required; carcinogenicity assessment accepted and ECAC agreed no studies needed
“The ECAC agreed with the Division that there was no need for additional nonclinical carcinogenicity studies for emicizumab on August 7, 2015.”
hERG / QT
No dedicated safety pharmacology; no CNS, respiratory or cardiovascular effects in monkey repeat-dose studies
“The safety pharmacology endpoints were evaluated during the repeated-dose toxicity studies described in Section 2.3.4 of this report. No effects on the CNS, respiratory or CNS were identified.”
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)
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)