Actemra
tocilizumab · IL-6RCynomolgus monkey only
Andembry: which tox species, and why?
garadacimab · Factor XIIa
Species
Mouse and cynomolgus monkey
“The Applicant characterized the toxicity profile of garadacimab by conducting 4-week mouse and 26-week monkey toxicology studies with garadacimab using the IV and SC routes.”
Why that species
Garadacimab cross-reacts with mouse, rabbit and cynomolgus βFXIIa
“Garadacimab affinity is cross reactive with mouse, rabbit and cynomolgus βFXIIa (700pM, 400pM and 19nM respectively).”
Surrogate molecule
No surrogate; the clinical antibody was tested in mice, cynomolgus monkeys and rabbits
“The Applicant characterized the toxicity profile of garadacimab by conducting 4-week mouse and 26-week monkey toxicology studies with garadacimab using the IV and SC routes.”
Species: general tox
Mouse (4-week) and cynomolgus monkey (26-week), IV and SC
“The Applicant characterized the toxicity profile of garadacimab by conducting 4-week mouse and 26-week monkey toxicology studies with garadacimab using the IV and SC routes.”
Species: DART
Rabbit (male and female fertility, EFD, pre/postnatal development)
“The potential reproductive toxicity of garadacimab was evaluated in fertility and early embryonic development studies with male and female rabbits, an embryofetal development study with female rabbits, and a pre- and postnatal development study with female rabbits.”
Species: carcinogenicity
Not conducted; rodent carcinogenicity study not technically feasible
“Based on the weight of evidence, the Division agreed with the Applicant that a rodent carcinogenicity study was not technically feasible.”
Surrogate used in
No surrogate used; garadacimab cross-reacts with mouse, rabbit and cynomolgus FXIIa
“Garadacimab affinity is cross reactive with mouse, rabbit and cynomolgus βFXIIa (700pM, 400pM and 19nM respectively).”
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)
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
Cablivi
caplacizumab · von Willebrand factor (A1 domain)Guinea pig and cynomolgus monkey
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