Actemra
tocilizumab · IL-6RNo special hazard in conventional genotoxicity studies
Keytruda: genotox, carcinogenicity and repro: done or skipped?
pembrolizumab · PD-1
Genotoxicity
Not conducted (ICH S6)
“Consistent with the ICH S6 guidance, genetic toxicology studies were not conducted or required for pembrolizumab.”
Carcinogenicity
Not conducted; not required for a product to treat advanced cancer; not planned as a post-marketing requirement
“Carcinogenicity studies were not required to support the licensing application for a product to treat advanced human cancer and are neither planned nor expected as post-marketing requirements at this time.”
Reproductive & developmental
Not conducted; dedicated embryofetal studies not warranted for the intended patient population
“Dedicated nonclinical studies investigating the effects of pembrolizumab on embryofetal development are not warranted at this time to support its use in the intended patient population.”
Safety pharmacology
Evaluated within the 1- and 6-month repeat-dose monkey studies
“safety pharmacology was evaluated as part of the 1-month and 6-months repeat-dose toxicity study in cynomolgus monkeys”
Same question, other monoclonal antibodies
Adakveo
crizanlizumab · P-selectinNot conducted (ICH S6)
Adbry
tralokinumab · IL-13Not conducted (ICH S6(R1))
Aduhelm
aducanumab · Aggregated amyloid-βNot conducted; antibodies unable to interact with genetic material
Aimovig
erenumab · CGRP receptorNot conducted (ICH S6(R1))
Ajovy
fremanezumab · CGRPNot conducted (ICH S6(R1))
Alhemo
concizumab · TFPINot conducted (ICH S6(R1))
Andembry
garadacimab · Factor XIIaNot conducted (ICH S6(R1))
Anthim
obiltoxaximab · B. anthracis PANot conducted
Arzerra
ofatumumab · CD20Not conducted (ICH S6)
Avastin
bevacizumab · VEGF-ANot conducted
Bavencio
avelumab · PD-L1Not conducted (ICH S6)
Benlysta
belimumab · BLyS (BAFF)Not conducted; not required for a monoclonal antibody
Beovu
brolucizumab · VEGF-ANot conducted (ICH S6(R1))
Beyfortus
nirsevimab · RSV F proteinNot conducted (ICH S6(R1))
Bimzelx
bimekizumab · IL-17A/IL-17FNot conducted (ICH S6(R1))
Briumvi
ublituximab · CD20Not recommended for biologics; an Ames assay was conducted and was negative
Cablivi
caplacizumab · von Willebrand factor (A1 domain)Not conducted (ICH S6(R1))
Campath
alemtuzumab · CD52Not conducted (ICH S6)
Cimzia
certolizumab pegol · TNF-αConducted: negative in Ames, human lymphocyte chromosomal aberration and mouse micronucleus assays
Cinqair
reslizumab · IL-5Not applicable for a protein; Ames and in vitro chromosomal aberration assays negative
Cosentyx
secukinumab · IL-17ANot conducted (ICH S6(R1))
Crysvita
burosumab · FGF23Not conducted (not appropriate for monoclonal antibodies)
Cyramza
ramucirumab · VEGFR2Not conducted (ICH S6)
Danyelza
naxitamab · GD2Not conducted (ICH S6/S9, advanced cancer)
Darzalex
daratumumab · CD38Not conducted (ICH S6)
Dupixent
dupilumab · IL-4RaNot conducted (ICH S6)
Ebanga
ansuvimab · Zaire ebolavirus glycoproteinNot conducted (ICH S6(R1))
Ebglyss
lebrikizumab · IL-13Not conducted (ICH S6)
Emgality
galcanezumab · CGRPNot conducted (ICH S6(R1))
Empliciti
elotuzumab · SLAMF7Not conducted (ICH S6)
Enflonsia
clesrovimab · RSV F protein (site IV)Not conducted (ICH S6(R1))
Enjaymo
sutimlimab · Complement C1sNot conducted (monoclonal antibody, ICH S6)
Enspryng
satralizumab · IL-6RNot conducted (antibodies unable to interact with genetic material)
Entyvio
vedolizumab · α4β7-integrinNot conducted (ICH S6(R1))
Erbitux
cetuximab · EGFRConducted (partial): Ames test and rat micronucleus test negative
Evenity
romosozumab · SclerostinNot conducted (recombinant protein not expected to interact with DNA)
Evkeeza
evinacumab · ANGPTL3Not conducted (ICH S6)
Exdensur
depemokimab · IL-5Not conducted (ICH S6(R1))
Fasenra
benralizumab · IL-5RαNot conducted; not applicable to a therapeutic protein
Gamifant
emapalumab · IFN-γNot conducted (ICH S6)
Gazyva
obinutuzumab · CD20Not conducted (ICH S6/S9)
Herceptin
trastuzumab · HER2Conducted: Ames, E. coli, human lymphocyte chromosome aberration and mouse micronucleus; all negative
Humira
adalimumab · TNF-αLimited tests (bacterial mutation, mouse micronucleus) negative; not needed for a monoclonal antibody (ICH S6)
Hympavzi
marstacimab · TFPINot conducted; not scientifically appropriate for a monoclonal antibody
Ilaris
canakinumab · IL-1βNot conducted (protein; ICH S6)
Ilumya
tildrakizumab · IL-23 p19Not conducted (ICH S6(R1))
Imaavy
nipocalimab · FcRnNot conducted
Imfinzi
durvalumab · PD-L1Not conducted
Imjudo
tremelimumab · CTLA-4Not conducted (ICH S6(R1))
Jemperli
dostarlimab · PD-1Not conducted; not warranted for a biotechnology-derived product
Kevzara
sarilumab · IL-6RNot conducted (not applicable to a monoclonal antibody)
Kisunla
donanemab · Amyloid-β (N3pG)Not conducted; antibodies unable to interact with genetic material
Lartruvo
olaratumab · PDGFRαNot conducted (ICH S6)
Leqembi
lecanemab · Amyloid-β protofibrilsNot conducted (ICH S6)
Libtayo
cemiplimab · PD-1Not conducted (ICH S6)
Loqtorzi
toripalimab · PD-1Not conducted (ICH S6(R1))
Lucentis
ranibizumab · VEGF-ANot conducted; acceptable given nature of compound
Margenza
margetuximab · HER2Not conducted (ICH S6(R1))
Monjuvi
tafasitamab · CD19Not conducted (ICH S6)
Nemluvio
nemolizumab · IL-31RANot conducted (ICH S6(R1))
Niktimvo
axatilimab · CSF-1RNot conducted; antibodies not expected to interact with DNA
Nucala
mepolizumab · IL-5Not conducted; not applicable to a therapeutic biologic protein
Ocrevus
ocrelizumab · CD20Not conducted (ICH S6)
Omvoh
mirikizumab · IL-23 p19Not conducted (ICH S6(R1))
Opdivo
nivolumab · PD-1Not conducted (ICH S6)
Pasatru
garetosmab · Activin ANot evaluated; monoclonal antibodies not expected to alter DNA or chromosomes
Penpulimab
penpulimab · PD-1Not conducted (ICH S6)
Perjeta
pertuzumab · HER2Not conducted (ICH S6)
Piasky
crovalimab · Complement C5Not conducted (biotechnology-derived pharmaceutical)
Portrazza
necitumumab · EGFRNot conducted (ICH S6)
Poteligeo
mogamulizumab · CCR4Not conducted (ICH S6(R1))
Praluent
alirocumab · PCSK9Not conducted (ICH S6); not expected to interact with DNA
Praxbind
idarucizumab · DabigatranNot conducted
Prolia
denosumab · RANKLNot conducted; not necessary for a recombinant protein
Raxibacumab
raxibacumab · B. anthracis protective antigenNot conducted
Remicade
infliximab · TNF-αComplete battery performed despite limited value; no genotoxic activity
Repatha
evolocumab · PCSK9Not conducted (ICH S6)
Rituxan
rituximab · CD20Not conducted; omission considered justified
Rystiggo
rozanolixizumab · FcRnNot conducted
Saphnelo
anifrolumab · IFNAR1Not conducted (ICH S6(R1))
Sarclisa
isatuximab · CD38Not conducted (ICH S6)
Siliq
brodalumab · IL-17RANot conducted (ICH S6)
Simponi
golimumab · TNF-αNot conducted
Simulect
basiliximab · IL-2Rα (CD25)Negative in Ames and V79 Chinese hamster cell chromosomal aberration assays
Skyrizi
risankizumab · IL-23 p19Not conducted (ICH S6(R1))
Soliris
eculizumab · Complement C5Not conducted (ICH S6)
Spevigo
spesolimab · IL-36RNot conducted
Stelara
ustekinumab · IL-12/23 p40Not conducted
Sylvant
siltuximab · IL-6Not conducted (ICH S6)
Synagis
palivizumab · RSV F proteinNot conducted
Takhzyro
lanadelumab · Plasma kallikreinNot conducted (ICH S6)
Taltz
ixekizumab · IL-17ANot conducted (ICH S6)
Tecentriq
atezolizumab · PD-L1Not conducted (ICH S6(R1))
Tepezza
teprotumumab · IGF-1RNot conducted (ICH S6(R1))
Tevimbra
tislelizumab · PD-1Not conducted (ICH S9)
Tezspire
tezepelumab · TSLPNot conducted (ICH S6(R1))
Tremfya
guselkumab · IL-23 p19Not conducted (ICH S6R1)
Trogarzo
ibalizumab · CD4Not conducted (ICH S6(R1))
Tysabri
natalizumab · α4-integrinStandard mutagenicity assays: no mutagenic potential
Tzield
teplizumab · CD3Not conducted
Ultomiris
ravulizumab · Complement C5Not conducted (ICH S6(R1))
Unituxin
dinutuximab · GD2Not conducted (ICH S6)
Unloxcyt
cosibelimab · PD-L1Not conducted (ICH S6(R1)); large molecule not expected to interact with DNA
Uplizna
inebilizumab · CD19Not conducted (ICH S6)
Vectibix
panitumumab · EGFRNot conducted
Veopoz
pozelimab · Complement C5Not conducted (ICH S6(R1))
Voyxact
sibeprenlimab · APRILNot conducted (antibody lacks ability to interact directly with DNA)
Vyepti
eptinezumab · CGRPNot conducted (ICH S6(R1))
Vyloy
zolbetuximab · Claudin 18.2Not conducted (ICH S6 and S9)
Xolair
omalizumab · IgEAmes test negative; full genotoxicity battery not conducted (no relevant species)
Yartemlea
narsoplimab · MASP-2Not conducted
Yervoy
ipilimumab · CTLA-4Not conducted
Zinbryta
daclizumab · IL-2Rα (CD25)Not conducted; antibody not expected to interact directly with DNA
Zinplava
bezlotoxumab · C. difficile toxin BNot conducted
Zynyz
retifanlimab · PD-1Not conducted; not warranted