Actemra
tocilizumab · IL-6RCynomolgus monkey only
Evkeeza: which tox species, and why?
evinacumab · ANGPTL3
Species
Cynomolgus monkey, rat and rabbit
“The toxicology profile of evinacumab was evaluated in rats, monkeys and rabbits, which are pharmacologically relevant nonclinical species”
Why that species
High sequence homology (83-98%) to human ANGPTL3 and evinacumab target binding in monkey, rabbit and rat
“The cynomolgus monkey, rabbit, and rat are pharmacologically relevant species for toxicologic evaluation of evinacumab considering the high sequence homology (83-98%) to human ANGPTL3 and evinacumab target binding data”
Surrogate molecule
No surrogate; the clinical antibody was tested in rats, monkeys and rabbits
“The toxicology profile of evinacumab was evaluated in rats, monkeys and rabbits, which are pharmacologically relevant nonclinical species”
Species: general tox
Rat (13-week) and cynomolgus monkey (26-week)
“All studies were previously reviewed, and the results of pivotal 13-week rat and 26-week monkey studies are summarized below.”
Species: DART
Rat (female fertility/pre- and postnatal, EFD), rabbit (EFD, male fertility) and monkey fertility endpoints in 26-week study
“The reproductive toxicity of evinacumab was assessed using male and female fertility endpoints collected from the chronic 26-week monkey toxicity study, and by conducting combined female fertility/early embryonic/pre and postnatal development study in rats, embryofetal development studies in rats and rabbits, and a male fertility and paternally-mediated EFD study in male rabbits.”
Species: carcinogenicity
Not conducted (weight-of-evidence assessment accepted)
“No in vivo animal carcinogenicity studies were requested by the Division after consulting with CDER’s Executive Carcinogenicity Assessment Committee (April 18, 2017) and the sponsor’s carcinogenicity assessment is considered adequate.”
Surrogate used in
No surrogate used; evinacumab tested in rats, monkeys and rabbits
“The toxicology profile of evinacumab was evaluated in rats, monkeys and rabbits, which are pharmacologically relevant nonclinical species”
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
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
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