Actemra
tocilizumab · IL-6RCynomolgus monkey only
Cablivi: which tox species, and why?
caplacizumab · von Willebrand factor (A1 domain)
Species
Guinea pig and cynomolgus monkey
“The toxicology of caplacizumab was evaluated in single and repeat-dose toxicity studies in both rodent (guinea pig) and non-rodent species (Cynomolgus monkey).”
Why that species
Cross-reactive with cynomolgus monkey and guinea pig vWF; no pharmacological activity in rats, mice or dogs
“Caplacizumab is cross-reactive to vWF in Cynomolgus monkey and guinea pig, but displays no pharmacological activity in rats, mice and dog.”
Surrogate molecule
No surrogate; the clinical Nanobody was tested in guinea pig and cynomolgus monkey
“This shows that caplacizumab is pharmacologically active in both species used for toxicity testing and that the animals were sufficiently exposed”
Species: general tox
Guinea pig and cynomolgus monkey
“The toxicology of caplacizumab was evaluated in single and repeat-dose toxicity studies in both rodent (guinea pig) and non-rodent species (Cynomolgus monkey).”
Species: DART
Guinea pig (embryo-fetal development by i.m. dosing, plus placental-transfer TK study)
“To support clinical development in women of child bearing potential a formal segment II study on embryo-foetal development was conducted in guinea pigs by i.m. administration and a follow-up TK study to assess placental transfer as well as maternal and foetal plasma levels of caplacizumab.”
Species: carcinogenicity
Not conducted (ICH S6(R1))
“In line with ICH S6(R1), no carcinogenicity studies have been performed.”
Surrogate used in
No surrogate used; clinical Nanobody pharmacologically active in both toxicity species
“This shows that caplacizumab is pharmacologically active in both species used for toxicity testing and that the animals were sufficiently exposed”
Same question, other monoclonal antibodies
Adakveo
crizanlizumab · P-selectinCynomolgus monkey only
Adbry
tralokinumab · IL-13Cynomolgus monkey only
Aduhelm
aducanumab · Aggregated amyloid-βCynomolgus monkey and transgenic Tg2576 mouse (murine surrogate and aducanumab); rat for reproductive studies
Aimovig
erenumab · CGRP receptorCynomolgus monkey only
Ajovy
fremanezumab · CGRPRat and cynomolgus monkey (chronic study in monkey only)
Alhemo
concizumab · TFPICynomolgus monkey only (rabbit used for efficacy and PK/PD)
Andembry
garadacimab · Factor XIIaMouse and cynomolgus monkey
Anthim
obiltoxaximab · B. anthracis PARat and cynomolgus monkey
Arzerra
ofatumumab · CD20Cynomolgus monkey only
Avastin
bevacizumab · VEGF-ACynomolgus monkey and rabbit
Bavencio
avelumab · PD-L1Cynomolgus monkey only
Benlysta
belimumab · BLyS (BAFF)Cynomolgus monkey only
Beovu
brolucizumab · VEGF-ACynomolgus monkey only
Beyfortus
nirsevimab · RSV F proteinCynomolgus monkey only
Bimzelx
bimekizumab · IL-17A/IL-17FCynomolgus monkey only
Briumvi
ublituximab · CD20Cynomolgus monkey only
Campath
alemtuzumab · CD52Cynomolgus monkey (general toxicity); huCD52 transgenic mouse (reproductive toxicity)
Cimzia
certolizumab pegol · TNF-αCynomolgus monkey (main species)
Cinqair
reslizumab · IL-5Mouse and cynomolgus monkey
Cosentyx
secukinumab · IL-17ACynomolgus monkey only
Crysvita
burosumab · FGF23Rabbit and cynomolgus monkey
Cyramza
ramucirumab · VEGFR2Cynomolgus monkey only
Danyelza
naxitamab · GD2Nude rat (athymic) only
Darzalex
daratumumab · CD38Chimpanzee (pivotal); cynomolgus monkey with surrogate antibody (supportive)
Dupixent
dupilumab · IL-4RaCynomolgus monkey only (surrogate REGN646); mouse fertility study with surrogate REGN1103
Ebanga
ansuvimab · Zaire ebolavirus glycoproteinRhesus monkey only
Ebglyss
lebrikizumab · IL-13Cynomolgus monkey only
Emgality
galcanezumab · CGRPRat and cynomolgus monkey
Empliciti
elotuzumab · SLAMF7None relevant; only a single-dose rhesus monkey study for off-target toxicity
Enflonsia
clesrovimab · RSV F protein (site IV)Rat only
Enjaymo
sutimlimab · Complement C1sCynomolgus monkey only
Enspryng
satralizumab · IL-6RCynomolgus monkey only
Entyvio
vedolizumab · α4β7-integrinRabbit and cynomolgus monkey
Erbitux
cetuximab · EGFRCynomolgus monkey (pivotal); supporting 4-week rat study
Evenity
romosozumab · SclerostinRat and cynomolgus monkey
Evkeeza
evinacumab · ANGPTL3Cynomolgus monkey, rat and rabbit
Exdensur
depemokimab · IL-5Cynomolgus monkey only
Fasenra
benralizumab · IL-5RαCynomolgus monkey only
Gamifant
emapalumab · IFN-γCynomolgus monkey only
Gazyva
obinutuzumab · CD20Cynomolgus monkey only
Herceptin
trastuzumab · HER2Rhesus and cynomolgus monkey
Humira
adalimumab · TNF-αCynomolgus monkey only (pivotal repeat-dose)
Hympavzi
marstacimab · TFPIRat and cynomolgus monkey
Ilaris
canakinumab · IL-1βMarmoset monkey only (plus mouse with surrogate antibody)
Ilumya
tildrakizumab · IL-23 p19Cynomolgus monkey only
Imaavy
nipocalimab · FcRnCynomolgus monkey only
Imfinzi
durvalumab · PD-L1Cynomolgus monkey only
Imjudo
tremelimumab · CTLA-4Cynomolgus monkey only
Jemperli
dostarlimab · PD-1Cynomolgus monkey only
Kevzara
sarilumab · IL-6RCynomolgus monkey only
Keytruda
pembrolizumab · PD-1Cynomolgus monkey only
Kisunla
donanemab · Amyloid-β (N3pG)Cynomolgus monkey and PDAPP transgenic mouse (surrogate antibody)
Lartruvo
olaratumab · PDGFRαCynomolgus monkey only
Leqembi
lecanemab · Amyloid-β protofibrilsCynomolgus monkey only
Libtayo
cemiplimab · PD-1Cynomolgus monkey only
Loqtorzi
toripalimab · PD-1Cynomolgus monkey only
Lucentis
ranibizumab · VEGF-ACynomolgus monkey (repeat-dose); rabbit for single-dose ocular studies
Margenza
margetuximab · HER2Cynomolgus monkey only
Monjuvi
tafasitamab · CD19Cynomolgus monkey only
Nemluvio
nemolizumab · IL-31RACynomolgus monkey only
Niktimvo
axatilimab · CSF-1RCynomolgus monkey only
Nucala
mepolizumab · IL-5Cynomolgus monkey (clinical antibody); mouse with surrogate antibody for fertility/EFD
Ocrevus
ocrelizumab · CD20Cynomolgus monkey only
Omvoh
mirikizumab · IL-23 p19Cynomolgus monkey only
Opdivo
nivolumab · PD-1Cynomolgus monkey only
Pasatru
garetosmab · Activin ARat and cynomolgus monkey
Penpulimab
penpulimab · PD-1Cynomolgus monkey only
Perjeta
pertuzumab · HER2Cynomolgus monkey only
Piasky
crovalimab · Complement C5Cynomolgus monkey only
Portrazza
necitumumab · EGFRCynomolgus monkey only
Poteligeo
mogamulizumab · CCR4Cynomolgus monkey only
Praluent
alirocumab · PCSK9Rat and cynomolgus monkey
Praxbind
idarucizumab · DabigatranRat and rhesus monkey
Prolia
denosumab · RANKLCynomolgus monkey only
Raxibacumab
raxibacumab · B. anthracis protective antigenHealthy rabbit and cynomolgus monkey
Remicade
infliximab · TNF-αChimpanzee (limited studies) and mouse (surrogate anti-mouse TNF-α antibody)
Repatha
evolocumab · PCSK9Hamster and cynomolgus monkey
Rituxan
rituximab · CD20Cynomolgus monkey only
Rystiggo
rozanolixizumab · FcRnCynomolgus monkey only
Saphnelo
anifrolumab · IFNAR1Cynomolgus monkey only
Sarclisa
isatuximab · CD38Cynomolgus monkey only (non-binding species, off-target toxicity assessment)
Siliq
brodalumab · IL-17RACynomolgus monkey only
Simponi
golimumab · TNF-αCynomolgus monkey only (mouse surrogate for supportive studies)
Simulect
basiliximab · IL-2Rα (CD25)Rhesus and cynomolgus monkey (primates only)
Skyrizi
risankizumab · IL-23 p19Cynomolgus monkey only
Soliris
eculizumab · Complement C5Mouse (surrogate antibody) only
Spevigo
spesolimab · IL-36RMouse (surrogate antibody) only
Stelara
ustekinumab · IL-12/23 p40Cynomolgus monkey only
Sylvant
siltuximab · IL-6Cynomolgus monkey only (fertility in mice with surrogate antibody)
Synagis
palivizumab · RSV F proteinNo repeat-dose studies; single-dose studies in rat and cynomolgus monkey only
Takhzyro
lanadelumab · Plasma kallikreinRat and cynomolgus monkey (monkey only for chronic study)
Taltz
ixekizumab · IL-17ACynomolgus monkey only
Tecentriq
atezolizumab · PD-L1Cynomolgus monkey (pivotal); mouse pilot study
Tepezza
teprotumumab · IGF-1RCynomolgus monkey only
Tevimbra
tislelizumab · PD-1Cynomolgus monkey only
Tezspire
tezepelumab · TSLPCynomolgus monkey only
Tremfya
guselkumab · IL-23 p19Cynomolgus monkey only
Trogarzo
ibalizumab · CD4Rhesus and cynomolgus monkey
Tysabri
natalizumab · α4-integrinCynomolgus monkey (repeat-dose); guinea pig and monkey for reproductive toxicity
Tzield
teplizumab · CD3Mouse (surrogate antibody) for repeat-dose and DART; single-dose chimpanzee study with teplizumab
Ultomiris
ravulizumab · Complement C5Mouse (surrogate antibody) only
Unituxin
dinutuximab · GD2Rat (repeat-dose) and cynomolgus monkey (single-dose safety pharmacology)
Unloxcyt
cosibelimab · PD-L1Cynomolgus monkey only
Uplizna
inebilizumab · CD19Human CD19 transgenic mouse only
Vectibix
panitumumab · EGFRCynomolgus monkey only
Veopoz
pozelimab · Complement C5Cynomolgus monkey only; not evaluated in rodents
Voyxact
sibeprenlimab · APRILCynomolgus monkey only
Vyepti
eptinezumab · CGRPRat, cynomolgus monkey and rabbit
Vyloy
zolbetuximab · Claudin 18.2Mouse and cynomolgus monkey
Xolair
omalizumab · IgECynomolgus monkey (pivotal); 4-week mouse study also conducted
Yartemlea
narsoplimab · MASP-2Mouse and cynomolgus monkey
Yervoy
ipilimumab · CTLA-4Cynomolgus monkey only
Zinbryta
daclizumab · IL-2Rα (CD25)Cynomolgus monkey only
Zinplava
bezlotoxumab · C. difficile toxin BMouse only
Zynyz
retifanlimab · PD-1Cynomolgus monkey only