Accrufer
ferric maltol · Iron replacementDog
Azstarys: which tox species, and why?
serdexmethylphenidate and dexmethylphenidate · Dopamine/norepinephrine reuptake
Species
Rat and dog (28-day); rabbit (6-month juvenile, EFD)
“The Division agreed to review 28-day repeat-dose toxicology data in two species, an embryo-fetal development study in the rabbit, and 6- month juvenile rabbit study to support this position.”
Why that species
Rabbit chosen by cross-species PK analysis as having the highest SDX exposure relative to humans (minimizing d-MPH exposure)
“In order to use the species with the highest SDX exposure compared to humans in the pivotal embryo-fetal development study and the 6-month juvenile animal study, a cross-species analysis was conducted, and the rabbit was determined to be the most appropriate species.”
Surrogate molecule
No surrogate; the clinical compound (SDX) was tested, with d-MPH as comparator
“In rat and dog single- and repeat-dose toxicology studies of up to 28-day duration of oral SDX with d-MPH as a comparator”
Species: general tox
Rat and dog (28-day); juvenile rabbit (6-month)
“there were no unique, adverse findings for SDX compared to d-MPH in 28-day repeat-dose toxicology studies in rat and dog, embryo-fetal development study in rabbits, and 6-month juvenile animal study in rabbits”
Species: DART
Rabbit only (EFD and 6-month juvenile study)
“there were no unique, adverse findings for SDX compared to d-MPH in 28-day repeat-dose toxicology studies in rat and dog, embryo-fetal development study in rabbits, and 6-month juvenile animal study in rabbits”
Species: carcinogenicity
Not conducted with SDX; relies on referenced d-MPH labeling
“Carcinogenicity studies were not conducted with SDX. The Applicant is relying upon the carcinogenicity data in the referenced product labeling.”
Surrogate used in
No surrogate used; SDX tested directly with d-MPH as comparator
“In rat and dog single- and repeat-dose toxicology studies of up to 28-day duration of oral SDX with d-MPH as a comparator”
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
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)
Lumakras
sotorasib · KRAS G12CRat and dog
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