Accrufer
ferric maltol · Iron replacementDog
Lumakras: which tox species, and why?
sotorasib · KRAS G12C
Species
Rat and dog
“The Applicant evaluated the safety of sotorasib using Sprague-Dawley rats and Beagle dogs in GLP-compliant repeat-dose toxicology studies of up to 3 months duration.”
Why that species
Human metabolites formed in vitro were also produced by rat and dog liver microsomes/hepatocytes
“The human metabolites formed in vitro were also produced in the rat and dog in vitro (liver microsomes/hepatocytes).”
Surrogate molecule
No surrogate; the clinical compound was tested
“The Applicant evaluated the safety of sotorasib using Sprague-Dawley rats and Beagle dogs in GLP-compliant repeat-dose toxicology studies of up to 3 months duration.”
Species: general tox
Rat and dog (3-month GLP studies)
“The Applicant evaluated the safety of sotorasib using Sprague-Dawley rats and Beagle dogs in GLP-compliant repeat-dose toxicology studies of up to 3 months duration.”
Species: DART
Rat and rabbit (EFD)
“The Applicant conducted GLP-compliant embryo-fetal development studies in Sprague-Dawley rats and New Zealand White rabbits.”
Species: carcinogenicity
Not conducted (advanced cancer indication, ICH S9)
“No carcinogenicity studies have been conducted nor are any planned in accordance with International Council for Harmonisation (ICH) S9 (ICH, 2009).”
Surrogate used in
No surrogate used; sotorasib tested directly in rats and dogs
“The Applicant evaluated the safety of sotorasib using Sprague-Dawley rats and Beagle dogs in GLP-compliant repeat-dose toxicology studies of up to 3 months duration.”
Same question, other small molecules
Adquey
difamilast · PDE4 (topical)Rat, dog and minipig
Agamree
vamorolone · Glucocorticoid receptor (dissociative)Mouse and dog
Alyftrek
vanzacaftor, tezacaftor and deutivacaftor · CFTRRat and dog
Anzupgo
delgocitinib · Pan-JAK (topical)Rat and dog (oral); minipig and mouse (dermal)
Aqneursa
levacetylleucine · Neuronal metabolism (proposed)Rat and dog
Artesunate
artesunate · Plasmodium (antimalarial)Rat and dog
Attruby
acoramidis · Transthyretin (stabiliser)Rat and dog
Augtyro
repotrectinib · ROS1/TRKRat and cynomolgus monkey
Avmapki Fakzynja Co-pack
avutometinib and defactinib · RAF/MEK clamp; FAKRat and monkey (avutometinib); rat and dog (defactinib)
Ayvakit
avapritinib · KIT/PDGFRARat and dog
Azstarys
serdexmethylphenidate and dexmethylphenidate · Dopamine/norepinephrine reuptakeRat and dog (28-day); rabbit (6-month juvenile, EFD)
Balversa
erdafitinib · FGFR1-4Rat and dog
Barhemsys
amisulpride · Dopamine D2/D3 receptorRat
Baxfendy
baxdrostat · Aldosterone synthase (CYP11B2)Rat and cynomolgus monkey
Beqalzi
sonrotoclax · BCL-2Mouse and dog
Blujepa
gepotidacin · Bacterial topoisomerases (gyrase/topo IV)Rat and dog
Brenzavvy
bexagliflozin · SGLT2Rat and monkey
Brexafemme
ibrexafungerp · Fungal glucan synthaseRat and dog
Brinsupri
brensocatib · DPP1 (cathepsin C)Rat and dog
Brukinsa
zanubrutinib · BTKRat and dog
Byfavo
remimazolam · GABA-A receptor (benzodiazepine site)Cynomolgus monkey and minipig
Bylvay
odevixibat · IBATRat and dog
Cabenuva
cabotegravir and rilpivirine · HIV-1 integrase; NNRTIRat and monkey (cabotegravir)
Camzyos
mavacamten · Cardiac myosinRat and dog
Caplyta
lumateperone · 5-HT2A / D2 receptorRat and dog (mouse up to 3 months)
Cardamyst
etripamil · L-type calcium channelRat and cynomolgus monkey
Cibinqo
abrocitinib · JAK1Rat and cynomolgus monkey
Cobenfy
xanomeline and trospium · Muscarinic M1/M4 agonist; peripheral antagonistRat and monkey
Cosela
trilaciclib · CDK4/6Rat and dog
Crenessity
crinecerfont · CRF1 receptorRat and dog
Cypsedo
cipepofol · GABA-A receptorRat and dog
Daybue
trofinetide · IGF-1 tripeptide analogueRat and dog
Dayvigo
lemborexant · Orexin OX1/OX2 receptorsRat and monkey
Defencath
taurolidine and heparin · Antimicrobial catheter lockRat (14-day IV study) and mouse (single-dose IP study)
Dojolvi
triheptanoin · Anaplerotic energy substrateMinipig (GLP); published rat dietary study
Duvyzat
givinostat · Histone deacetylase (class I/II)Rat and monkey (supporting 13-week mouse and 4-week dog)
Egaten
triclabendazole · Fasciola (tubulin)Rat and dog
Ekterly
sebetralstat · Plasma kallikreinRat and cynomolgus monkey
Ensacove
ensartinib · ALKRat and dog
Evrysdi
risdiplam · SMN2 splicingRat and cynomolgus monkey
Exblifep
cefepime and enmetazobactam · PBPs; beta-lactamase (enmetazobactam)Rat and dog
Exkivity
mobocertinib · EGFR exon 20 insertionRat and dog
Exxua
gepirone · 5-HT1A receptorRat and dog
Fabhalta
iptacopan · Complement factor BRat and dog
Fetroja
cefiderocol · Penicillin-binding proteinsRat and monkey
Fexinidazole
fexinidazole · Trypanosoma bruceiRat and dog
Filspari
sparsentan · Endothelin A / angiotensin II receptorsMouse, rat and cynomolgus monkey
Fotivda
tivozanib · VEGFR1-3Rat and cynomolgus monkey
Foundayo
orforglipron · GLP-1 receptor (non-peptide)Rat and cynomolgus monkey
Fruzaqla
fruquintinib · VEGFR1-3Rat and dog
Gavreto
pralsetinib · RETRat and cynomolgus monkey
Gemtesa
vibegron · β3-adrenergic receptorRat and cynomolgus monkey
Gomekli
mirdametinib · MEK1/2Rat and dog
Grafapex
treosulfan · DNA alkylationRat, dog and monkey
Hernexeos
zongertinib · HER2 (mutant)Rat and dog
Hyrnuo
sevabertinib · HER2 (mutant)Rat and monkey
Ibsrela
tenapanor · NHE3Rat and dog
Ibtrozi
taletrectinib · ROS1Rat and cynomolgus monkey
Idvynso
doravirine and islatravir · NNRTI; NRTTIRat and rhesus monkey (islatravir), plus mouse up to 3 months
Inluriyo
imlunestrant · Estrogen receptor (SERD)Rat and cynomolgus monkey
Inpefa
sotagliflozin · SGLT1/SGLT2Rat and dog
Inqovi
decitabine and cedazuridine · DNMT (decitabine); cytidine deaminase (cedazuridine)Mouse and cynomolgus monkey (cedazuridine); rat (decitabine)
Inrebic
fedratinib · JAK2Rat and dog
Iqirvo
elafibranor · PPARα/δRat and cynomolgus monkey (mouse up to 3 months)
Isturisa
osilodrostat · 11β-hydroxylase (CYP11B1)Rat and dog
Itovebi
inavolisib · PI3Kα (mutant-selective)Rat and dog
Jascayd
nerandomilast · PDE4BRat, minipig and cynomolgus monkey
Jaypirca
pirtobrutinib · BTK (non-covalent)Rat and dog
Jesduvroq
daprodustat · HIF prolyl hydroxylaseRat and cynomolgus monkey (dog in studies up to 13 weeks)
Jideytro
zidesamtinib · ROS1Rat and dog
Joenja
leniolisib · PI3KδRat and cynomolgus monkey
Journavx
suzetrigine · NaV1.8Rat and cynomolgus monkey
Kerendia
finerenone · Mineralocorticoid receptorRat and dog
Klisyri
tirbanibulin · Tubulin / SrcRat and dog (oral); minipig and rat (topical)
Komzifti
ziftomenib · Menin-KMT2AMouse and dog
Koselugo
selumetinib · MEK1/2Mouse, rat and cynomolgus monkey
Krazati
adagrasib · KRAS G12CRat and dog
Kygevvi
doxecitine and doxribtimine · Pyrimidine nucleoside replacement (TK2 deficiency)Rat and dog (plus 4-week mouse)
Lampit
nifurtimox · Trypanosoma cruziRat and dog
Lazcluze
lazertinib · EGFR (mutant-selective)Rat and dog
Leqselvi
deuruxolitinib · JAK1/JAK2Rat and dog
Lifyorli
relacorilant · Glucocorticoid receptor (antagonist)Rat and cynomolgus monkey
Litfulo
ritlecitinib · JAK3/TEC kinasesRat and dog
Livdelzi
seladelpar · PPARδRat and cynomolgus monkey (also mouse and dog)
Livmarli
maralixibat · IBAT (ASBT)Rat and dog
Livtencity
maribavir · CMV UL97 protein kinaseRat and cynomolgus monkey (plus 13-week mouse)
Lupkynis
voclosporin · CalcineurinRat and cynomolgus monkey
Lybalvi
olanzapine and samidorphan · D2/5-HT2A; opioid receptors (samidorphan)Rat and dog
Lynavoy
linerixibat · IBATRat and dog
Lynkuet
elinzanetant · NK1/NK3 receptorsRat and cynomolgus monkey
Lytgobi
futibatinib · FGFR1-4 (covalent)Rat and dog
Mayzent
siponimod · S1P1/S1P5 receptorRat and cynomolgus monkey
Miebo
perfluorohexyloctane · Tear film evaporation barrierRabbit (ocular) and rat (oral)
Miplyffa
arimoclomol · Heat-shock response amplifierRat and dog
Modeyso
dordaviprone · DRD2 antagonist / ClpP agonistRat and dog
Myqorzo
aficamten · Cardiac myosinRat and dog
Nereus
tradipitant · NK1 receptorRat and dog (plus 13-week mouse)
Nexletol
bempedoic acid · ATP citrate lyaseRat and monkey
Nextstellis
drospirenone and estetrol · Estrogen / progestin receptorsRat and cynomolgus monkey
Nourianz
istradefylline · Adenosine A2A receptorRat and dog
Nubeqa
darolutamide · Androgen receptorRat and dog
Nulibry
fosdenopterin · cPMP replacement (MoCD type A)Rat and dog (juvenile)
Nurtec ODT
rimegepant · CGRP receptorRat and cynomolgus monkey
Nuzolvence
zoliflodacin · Bacterial topoisomerase IIRat and dog
Ogsiveo
nirogacestat · Gamma secretaseRat and dog
Ohtuvayre
ensifentrine · PDE3/PDE4Rat and dog
Ojemda
tovorafenib · RAF (type II pan-RAF)Rat and cynomolgus monkey
Ojjaara
momelotinib · JAK1/JAK2/ACVR1Rat and dog
Olinvyk
oliceridine · μ-opioid receptor (G-protein biased)Rat and monkey
Omlonti
omidenepag isopropyl · EP2 receptorRat and cynomolgus monkey
Ongentys
opicapone · COMTRat and cynomolgus monkey
Orgovyx
relugolix · GnRH receptorRat and cynomolgus monkey (mouse up to 13 weeks)
Orladeyo
berotralstat · Plasma kallikreinRat and monkey
Orlynvah
sulopenem etzadroxil and probenecid · Penicillin-binding proteinsRat and cynomolgus monkey
Orserdu
elacestrant · Estrogen receptor (SERD)Rat and cynomolgus monkey
Orzeyful
oveporexton · Orexin OX2 receptor agonistRat and cynomolgus monkey
Oxbryta
voxelotor · HbS polymerisationRat and cynomolgus monkey (also mouse)
Palsonify
paltusotine · Somatostatin receptor 2Rat and dog
Paxlovid
nirmatrelvir and ritonavir · SARS-CoV-2 Mpro (3CL protease)Rat and cynomolgus monkey
Pemazyre
pemigatinib · FGFR1-3Rat and cynomolgus monkey
Piqray
alpelisib · PI3KαRat and dog
Pizensy
lactitol · Osmotic laxativeRat and Tg.rasH2 mouse
Ponvory
ponesimod · S1P1 receptorRat and dog (mouse for carcinogenicity, rabbit for EFD)
Pretomanid
pretomanid · Mycobacterial cell wall / respirationRat and cynomolgus monkey
Pyrukynd
mitapivat · Pyruvate kinase (activator)Rat and cynomolgus monkey
Qelbree
viloxazine · Norepinephrine reuptakeRat and dog
Qinlock
ripretinib · KIT/PDGFRARat and dog
Qulipta
atogepant · CGRP receptorRat and rhesus monkey
Quviviq
daridorexant · Orexin OX1/OX2 receptorsRat and dog
Rapiblyk
landiolol · β1-adrenergic receptorRat and dog
Rasonque
daraxonrasib · RAS(ON) multi-selectiveMouse and cynomolgus monkey
Recarbrio
imipenem, cilastatin and relebactam · Beta-lactamase (relebactam)Rat and monkey
Relyvrio
sodium phenylbutyrate and taurursodiol · ER stress / mitochondrial (proposed)Rat and minipig
Retevmo
selpercatinib · RETRat and Göttingen minipig
Revtorpyk
gedatolisib · PI3K/mTORRat and dog
Revuforj
revumenib · Menin-KMT2ARat and dog
Reyvow
lasmiditan · 5-HT1F receptorRat and dog
Rezdiffra
resmetirom · Thyroid hormone receptor βRat and dog (plus mouse up to 3 months)
Rezlidhia
olutasidenib · IDH1 (mutant)Rat and cynomolgus monkey
Rezurock
belumosudil · ROCK2Rat and dog
Rezzayo
rezafungin · Fungal glucan synthaseRat and cynomolgus monkey
Rhapsido
remibrutinib · BTKRat and dog
Rinvoq
upadacitinib · JAK1Rat and dog
Romvimza
vimseltinib · CSF1RRat and dog
Rozlytrek
entrectinib · TRK/ROS1/ALKRat and dog
Rukobia
fostemsavir · HIV-1 gp120 (attachment)Rat and dog
Scemblix
asciminib · BCR-ABL1 (STAMP, myristoyl pocket)Rat and cynomolgus monkey (plus 4-week dog)
Sephience
sepiapterin · Tetrahydrobiopterin precursorRat and marmoset monkey
Simtriyo
centanafadine · Triple monoamine reuptakeRat and dog
Skyclarys
omaveloxolone · Nrf2 activatorRat and cynomolgus monkey
Sofdra
sofpironium · Muscarinic receptors (topical)Rat and Göttingen minipig
Sohonos
palovarotene · RARγRat and dog
Sotyktu
deucravacitinib · TYK2Rat and cynomolgus monkey
Sunlenca
lenacapavir · HIV-1 capsidRat and dog
Sunosi
solriamfetol · Dopamine/norepinephrine reuptakeRat and dog (plus 3-month mouse)
Tabrecta
capmatinib · METRat and cynomolgus monkey
Tavneos
avacopan · C5a receptor (C5aR1)Hamster, rat and cynomolgus monkey
Tazverik
tazemetostat · EZH2Rat and cynomolgus monkey
Tepmetko
tepotinib · METRat and dog
Trikafta
elexacaftor, tezacaftor and ivacaftor · CFTRRat and dog
Truqap
capivasertib · AKT1-3Rat and dog
Truseltiq
infigratinib · FGFR1-3Rat and dog
Tryptyr
acoltremon · TRPM8 agonistRabbit and dog (ocular); rat (intravenous)
Tryvio
aprocitentan · Endothelin A/B receptorsRat and dog
Tukysa
tucatinib · HER2Rat and cynomolgus monkey
Turalio
pexidartinib · CSF1RRat and dog
Ubrelvy
ubrogepant · CGRP receptorRat and rhesus monkey
Ukoniq
umbralisib · PI3Kδ / CK1εMouse and dog
Utebzi
tebipenem pivoxil · Penicillin-binding proteinsRat and cynomolgus monkey
Vafseo
vadadustat · HIF prolyl hydroxylaseRat and dog (plus 3-month mouse)
Vanflyta
quizartinib · FLT3Rat, dog and cynomolgus monkey
Vanrafia
atrasentan · Endothelin A receptorRat and dog
Veklury
remdesivir · SARS-CoV-2 RNA polymeraseRat and cynomolgus monkey
Velsipity
etrasimod · S1P1/S1P4/S1P5 receptorsRat and dog
Veozah
fezolinetant · Neurokinin-3 receptorRat and cynomolgus monkey (females)
Veppanu
vepdegestrant · Estrogen receptor (PROTAC degrader)Rat and dog
Verquvo
vericiguat · Soluble guanylate cyclaseRat and dog
Vivjoa
oteseconazole · Fungal CYP51Rat and dog
Vizz
aceclidine · Muscarinic agonist (miotic)Rabbit
Vonjo
pacritinib · JAK2/FLT3Mouse and dog
Voquezna
vonoprazan · H+/K+-ATPase (potassium-competitive)Rat and dog
Voranigo
vorasidenib · IDH1/IDH2Rat and cynomolgus monkey
Voydeya
danicopan · Complement factor DRat and dog
Vtama
tapinarof · Aryl hydrocarbon receptorRat and minipig
Vyndaqel
tafamidis · Transthyretin (stabiliser)Rat and dog
Wakix
pitolisant · Histamine H3 receptorRat and cynomolgus monkey (mouse up to 1 month)
Wayrilz
rilzabrutinib · BTK (reversible covalent)Rat and dog
Welireg
belzutifan · HIF-2αRat and dog
Winlevi
clascoterone · Androgen receptor (topical)Rat and minipig
Xacduro
sulbactam and durlobactam · PBPs; beta-lactamase (durlobactam)Rat and dog (mouse for embryo-fetal development)
Xcopri
cenobamate · Sodium channel / GABA-ARat and cynomolgus monkey (mouse up to 13 weeks)
Xdemvy
lotilaner · Mite GABA-Cl channelRabbit and dog (ocular); rat and dog (systemic)
Xeglyze
abametapir · Lice metalloproteinasesRat and minipig
Xenleta
lefamulin · Bacterial ribosome (50S PTC)Rat and cynomolgus monkey
Xocova
ensitrelvir · SARS-CoV-2 3CL proteaseRat and cynomolgus monkey
Xolremdi
mavorixafor · CXCR4Rat and dog
Xpovio
selinexor · XPO1Rat and cynomolgus monkey
Zavzpret
zavegepant · CGRP receptorRat and cynomolgus monkey
Zaynich
cefepime and zidebactam · PBPs; beta-lactam enhancer (zidebactam)Rat and dog
Zegfrovy
sunvozertinib · EGFR exon 20 insertionRat and dog
Zenbexus
iberdomide · Cereblon (CELMoD)Rat and monkey
Zeposia
ozanimod · S1P1/S1P5 receptorRat and cynomolgus monkey
Zepzelca
lurbinectedin · DNA minor groove (transcription)Rat, dog and cynomolgus monkey
Zevtera
ceftobiprole medocaril · Penicillin-binding proteinsRat, marmoset and dog
Zokinvy
lonafarnib · FarnesyltransferaseRat and cynomolgus monkey
Ztalmy
ganaxolone · GABA-A receptor (positive modulator)Rat and dog
Zulresso
brexanolone · GABA-A receptor (positive modulator)Rat and dog
Zurzuvae
zuranolone · GABA-A receptor (positive modulator)Rat and dog
Zycubo
copper histidinate · Copper replacement (Menkes disease)Juvenile rat only