Joenja (leniolisib): how long were the pivotal tox studies?

39 (39-week monkey) (Source: FDA multi-discipline review, p. 39.)

Atlas/Small molecules/Joenja/Study length

Joenja: how long were the pivotal tox studies?

leniolisib · PI3Kδ

Longest pivotal study

39 (39-week monkey)

“general toxicity studies with leniolisib were conducted in rats and monkeys with dosing durations up to 6 months in rodents and 9 months in non-rodents.”

✓ VerifiedFDA multi-discipline review, p. 39Source ↗

Pivotal GLP studies

26-week (6-month) rat and 39-week (9-month) monkey repeat-dose studies

“general toxicity studies with leniolisib were conducted in rats and monkeys with dosing durations up to 6 months in rodents and 9 months in non-rodents.”

✓ VerifiedFDA multi-discipline review, p. 39Source ↗

Route in tox

Oral gavage

“Monkeys (n=3/sex/group) were dosed once daily at 0, 30, 100, or 300 mg/kg/day via oral gavage for 14 days.”

✓ VerifiedFDA multi-discipline review, p. 41Source ↗

Same question, other small molecules

Accrufer

ferric maltol · Iron replacement

4 (28-day dog)

Adquey

difamilast · PDE4 (topical)

39 (39-week dog and minipig)

Agamree

vamorolone · Glucocorticoid receptor (dissociative)

39 (9-month dog)

Alyftrek

vanzacaftor, tezacaftor and deutivacaftor · CFTR

39 (39-week dog, vanzacaftor)

Anzupgo

delgocitinib · Pan-JAK (topical)

39 (9-month oral dog and dermal minipig)

Aqneursa

levacetylleucine · Neuronal metabolism (proposed)

39 (39-week dog)

Artesunate

artesunate · Plasmodium (antimalarial)

4 (28-day rat and dog)

Attruby

acoramidis · Transthyretin (stabiliser)

39 (39-week dog)

Augtyro

repotrectinib · ROS1/TRK

13 (91-day rat and monkey)

Avmapki Fakzynja Co-pack

avutometinib and defactinib · RAF/MEK clamp; FAK

13 (13-week rat, monkey and dog)

Ayvakit

avapritinib · KIT/PDGFRA

39 (9-month dog)

Azstarys

serdexmethylphenidate and dexmethylphenidate · Dopamine/norepinephrine reuptake

26 (6-month juvenile rabbit)

Balversa

erdafitinib · FGFR1-4

13 (13-week rat and dog)

Barhemsys

amisulpride · Dopamine D2/D3 receptor

4 (28-day rat)

Baxfendy

baxdrostat · Aldosterone synthase (CYP11B2)

39 (9-month monkey)

Beqalzi

sonrotoclax · BCL-2

13 weeks

Blujepa

gepotidacin · Bacterial topoisomerases (gyrase/topo IV)

13 (13-week rat and dog)

Brenzavvy

bexagliflozin · SGLT2

39 (39-week monkey)

Brexafemme

ibrexafungerp · Fungal glucan synthase

26 (26-week rat)

Brinsupri

brensocatib · DPP1 (cathepsin C)

39 (9-month dog)

Brukinsa

zanubrutinib · BTK

39 (9-month dog)

Byfavo

remimazolam · GABA-A receptor (benzodiazepine site)

4 (4-week minipig and monkey)

Bylvay

odevixibat · IBAT

39 (39-week dog)

Cabenuva

cabotegravir and rilpivirine · HIV-1 integrase; NNRTI

39 (39-week monkey)

Camzyos

mavacamten · Cardiac myosin

39 (9-month dog)

Caplyta

lumateperone · 5-HT2A / D2 receptor

39 (9-month dog)

Cardamyst

etripamil · L-type calcium channel

26 (6-month monkey)

Cibinqo

abrocitinib · JAK1

39 (9-month monkey)

Cobenfy

xanomeline and trospium · Muscarinic M1/M4 agonist; peripheral antagonist

52 (1-year monkey, xanomeline)

Cosela

trilaciclib · CDK4/6

1 (7-day rat and dog iv)

Crenessity

crinecerfont · CRF1 receptor

52 (12-month dog)

Cypsedo

cipepofol · GABA-A receptor

4 (rat and dog, dosing every other day)

Daybue

trofinetide · IGF-1 tripeptide analogue

39 (39-week dog)

Dayvigo

lemborexant · Orexin OX1/OX2 receptors

39 (9-month monkey)

Defencath

taurolidine and heparin · Antimicrobial catheter lock

2 (14-day rat; not considered pivotal)

Dojolvi

triheptanoin · Anaplerotic energy substrate

39 (9-month juvenile minipig)

Duvyzat

givinostat · Histone deacetylase (class I/II)

39 (39-week monkey)

Egaten

triclabendazole · Fasciola (tubulin)

13 (13-week rat and dog)

Ekterly

sebetralstat · Plasma kallikrein

26 (6-month rat and monkey)

Ensacove

ensartinib · ALK

13 (13-week rat and dog)

Evrysdi

risdiplam · SMN2 splicing

39 (39-week monkey)

Exblifep

cefepime and enmetazobactam · PBPs; beta-lactamase (enmetazobactam)

13 (13-week dog combination study)

Exkivity

mobocertinib · EGFR exon 20 insertion

13 (3-month rat and dog)

Exxua

gepirone · 5-HT1A receptor

52 (12-month dog)

Fabhalta

iptacopan · Complement factor B

39 (39-week dog)

Fetroja

cefiderocol · Penicillin-binding proteins

13 (3-month rat and monkey)

Fexinidazole

fexinidazole · Trypanosoma brucei

4 (28-day rat and dog)

Filspari

sparsentan · Endothelin A / angiotensin II receptors

39 (39-week monkey)

Fotivda

tivozanib · VEGFR1-3

39 (39-week monkey)

Foundayo

orforglipron · GLP-1 receptor (non-peptide)

39 (9-month monkey)

Fruzaqla

fruquintinib · VEGFR1-3

13 (13-week rat and dog GLP studies)

Gavreto

pralsetinib · RET

13 (13-week rat and monkey)

Gemtesa

vibegron · β3-adrenergic receptor

39 (9-month monkey)

Gomekli

mirdametinib · MEK1/2

13 (3-month rat and dog)

Grafapex

treosulfan · DNA alkylation

4 (4-week rat GLP study)

Hernexeos

zongertinib · HER2 (mutant)

13 (13-week rat and dog)

Hyrnuo

sevabertinib · HER2 (mutant)

13 (13-week rat and monkey)

Ibsrela

tenapanor · NHE3

39 (9-month dog)

Ibtrozi

taletrectinib · ROS1

12 (85-day rat and monkey)

Idvynso

doravirine and islatravir · NNRTI; NRTTI

39 (9-month monkey)

Inluriyo

imlunestrant · Estrogen receptor (SERD)

26 (6-month rat)

Inpefa

sotagliflozin · SGLT1/SGLT2

39 (39-week dog)

Inqovi

decitabine and cedazuridine · DNMT (decitabine); cytidine deaminase (cedazuridine)

13 (92-day monkey, 4 cycles)

Inrebic

fedratinib · JAK2

39 (9-month dog)

Iqirvo

elafibranor · PPARα/δ

52 (12-month monkey)

Isturisa

osilodrostat · 11β-hydroxylase (CYP11B1)

39 (39-week dog)

Itovebi

inavolisib · PI3Kα (mutant-selective)

13 (3-month rat and dog)

Jascayd

nerandomilast · PDE4B

39 (39-week minipig and monkey)

Jaypirca

pirtobrutinib · BTK (non-covalent)

13 (3-month rat and dog)

Jesduvroq

daprodustat · HIF prolyl hydroxylase

39 (39-week monkey)

Jideytro

zidesamtinib · ROS1

13 (13-week rat and dog)

Journavx

suzetrigine · NaV1.8

13 (13-week rat and monkey)

Kerendia

finerenone · Mineralocorticoid receptor

39 (9-month dog)

Klisyri

tirbanibulin · Tubulin / Src

4 (28-day oral rat and dog)

Komzifti

ziftomenib · Menin-KMT2A

13 (13-week mouse and dog)

Koselugo

selumetinib · MEK1/2

26 (26-week mouse and monkey)

Krazati

adagrasib · KRAS G12C

13 (13-week rat and dog)

Kygevvi

doxecitine and doxribtimine · Pyrimidine nucleoside replacement (TK2 deficiency)

26 (6-month juvenile rat)

Lampit

nifurtimox · Trypanosoma cruzi

52 (52-week dog)

Lazcluze

lazertinib · EGFR (mutant-selective)

13 (13-week rat and dog)

Leqselvi

deuruxolitinib · JAK1/JAK2

52 (52-week dog)

Lifyorli

relacorilant · Glucocorticoid receptor (antagonist)

39 (39-week monkey)

Litfulo

ritlecitinib · JAK3/TEC kinases

39 (39-week dog)

Livdelzi

seladelpar · PPARδ

52 (52-week monkey)

Livmarli

maralixibat · IBAT (ASBT)

52 (1-year dog)

Livtencity

maribavir · CMV UL97 protein kinase

52 (52-week monkey)

Lumakras

sotorasib · KRAS G12C

13 (3-month rat and dog)

Lupkynis

voclosporin · Calcineurin

39 (39-week monkey)

Lybalvi

olanzapine and samidorphan · D2/5-HT2A; opioid receptors (samidorphan)

39 (9-month dog, samidorphan)

Lynavoy

linerixibat · IBAT

39 (39-week dog)

Lynkuet

elinzanetant · NK1/NK3 receptors

39 (39-week monkey)

Lytgobi

futibatinib · FGFR1-4 (covalent)

13 (13-week rat and dog)

Mayzent

siponimod · S1P1/S1P5 receptor

52 (52-week monkey)

Miebo

perfluorohexyloctane · Tear film evaporation barrier

26 (26-week rabbit ocular)

Miplyffa

arimoclomol · Heat-shock response amplifier

52 (52-week dog)

Modeyso

dordaviprone · DRD2 antagonist / ClpP agonist

13 (13-week rat and dog)

Myqorzo

aficamten · Cardiac myosin

39 (39-week dog)

Nereus

tradipitant · NK1 receptor

26 (6-month rat)

Nexletol

bempedoic acid · ATP citrate lyase

52 (52-week monkey)

Nextstellis

drospirenone and estetrol · Estrogen / progestin receptors

39 (39-week monkey)

Nourianz

istradefylline · Adenosine A2A receptor

52 (52-week dog)

Nubeqa

darolutamide · Androgen receptor

39 (39-week dog)

Nulibry

fosdenopterin · cPMP replacement (MoCD type A)

39 (juvenile dog)

Nurtec ODT

rimegepant · CGRP receptor

39 (9-month monkey)

Nuzolvence

zoliflodacin · Bacterial topoisomerase II

4 (4-week rat and dog)

Ogsiveo

nirogacestat · Gamma secretase

13 (3-month rat and dog)

Ohtuvayre

ensifentrine · PDE3/PDE4

40 (40-week dog)

Ojemda

tovorafenib · RAF (type II pan-RAF)

13 (3-month rat and monkey)

Ojjaara

momelotinib · JAK1/JAK2/ACVR1

39 (39-week dog)

Olinvyk

oliceridine · μ-opioid receptor (G-protein biased)

4 (28-day rat)

Omlonti

omidenepag isopropyl · EP2 receptor

39 (39-week monkey topical ocular)

Ongentys

opicapone · COMT

52 (52-week monkey)

Orgovyx

relugolix · GnRH receptor

39 (39-week monkey)

Orladeyo

berotralstat · Plasma kallikrein

39 (9-month monkey)

Orlynvah

sulopenem etzadroxil and probenecid · Penicillin-binding proteins

4 (1-month rat and monkey)

Orserdu

elacestrant · Estrogen receptor (SERD)

39 (39-week monkey)

Orzeyful

oveporexton · Orexin OX2 receptor agonist

39 (39-week monkey)

Oxbryta

voxelotor · HbS polymerisation

39 (39-week monkey)

Palsonify

paltusotine · Somatostatin receptor 2

39 (9-month dog)

Paxlovid

nirmatrelvir and ritonavir · SARS-CoV-2 Mpro (3CL protease)

4 (1-month rat and monkey)

Pemazyre

pemigatinib · FGFR1-3

13 (3-month rat and monkey)

Piqray

alpelisib · PI3Kα

13 (13-week rat and dog)

Pizensy

lactitol · Osmotic laxative

13 (91-day rat)

Ponvory

ponesimod · S1P1 receptor

52 (52-week dog)

Pretomanid

pretomanid · Mycobacterial cell wall / respiration

39 (9-month monkey)

Pyrukynd

mitapivat · Pyruvate kinase (activator)

39 (9-month monkey)

Qelbree

viloxazine · Norepinephrine reuptake

78 (18-month rat)

Qinlock

ripretinib · KIT/PDGFRA

13 (13-week rat and dog)

Qulipta

atogepant · CGRP receptor

39 (9-month monkey)

Quviviq

daridorexant · Orexin OX1/OX2 receptors

39 (39-week dog)

Rapiblyk

landiolol · β1-adrenergic receptor

4 (4-week rat and dog studies)

Rasonque

daraxonrasib · RAS(ON) multi-selective

13 (13-week mouse and monkey)

Recarbrio

imipenem, cilastatin and relebactam · Beta-lactamase (relebactam)

13 (3-month rat and monkey)

Relyvrio

sodium phenylbutyrate and taurursodiol · ER stress / mitochondrial (proposed)

39 (9-month minipig)

Retevmo

selpercatinib · RET

13 weeks

Revtorpyk

gedatolisib · PI3K/mTOR

13 (3-month rat and dog)

Revuforj

revumenib · Menin-KMT2A

13 (13-week rat and dog)

Reyvow

lasmiditan · 5-HT1F receptor

39 (39-week dog)

Rezdiffra

resmetirom · Thyroid hormone receptor β

39 weeks

Rezlidhia

olutasidenib · IDH1 (mutant)

13 (13-week rat and monkey)

Rezurock

belumosudil · ROCK2

39 (39-week dog)

Rezzayo

rezafungin · Fungal glucan synthase

26 (26-week rat and monkey)

Rhapsido

remibrutinib · BTK

39 (39-week dog)

Rinvoq

upadacitinib · JAK1

39 (39-week dog)

Romvimza

vimseltinib · CSF1R

39 (39-week dog)

Rozlytrek

entrectinib · TRK/ROS1/ALK

13 (13-week rat and dog)

Rukobia

fostemsavir · HIV-1 gp120 (attachment)

39 (9-month dog)

Scemblix

asciminib · BCR-ABL1 (STAMP, myristoyl pocket)

39 (39-week monkey)

Sephience

sepiapterin · Tetrahydrobiopterin precursor

39 (39-week marmoset)

Simtriyo

centanafadine · Triple monoamine reuptake

43 (43-week juvenile dog)

Skyclarys

omaveloxolone · Nrf2 activator

39 (39-week monkey)

Sofdra

sofpironium · Muscarinic receptors (topical)

39 (39-week dermal minipig)

Sohonos

palovarotene · RARγ

39 (39-week dog)

Sotyktu

deucravacitinib · TYK2

39 (9-month monkey)

Sunlenca

lenacapavir · HIV-1 capsid

39 (9-month dog)

Sunosi

solriamfetol · Dopamine/norepinephrine reuptake

52 (12-month dog)

Tabrecta

capmatinib · MET

13 (13-week rat and monkey)

Tavneos

avacopan · C5a receptor (C5aR1)

44 (44-week monkey)

Tazverik

tazemetostat · EZH2

13 (13-week rat and monkey)

Tepmetko

tepotinib · MET

39 (39-week dog)

Trikafta

elexacaftor, tezacaftor and ivacaftor · CFTR

39 (39-week dog, elexacaftor)

Truqap

capivasertib · AKT1-3

39 (9-month dog)

Truseltiq

infigratinib · FGFR1-3

39 (39-week dog)

Tryptyr

acoltremon · TRPM8 agonist

26 (6-month rabbit and dog ocular)

Tryvio

aprocitentan · Endothelin A/B receptors

39 (39-week dog)

Tukysa

tucatinib · HER2

13 weeks

Turalio

pexidartinib · CSF1R

39 (9-month dog)

Ubrelvy

ubrogepant · CGRP receptor

39 (9-month monkey)

Ukoniq

umbralisib · PI3Kδ / CK1ε

39 (39-week dog)

Utebzi

tebipenem pivoxil · Penicillin-binding proteins

4 (28-day GLP rat and monkey; non-GLP studies up to 90 days)

Vafseo

vadadustat · HIF prolyl hydroxylase

39 (9-month dog)

Vanflyta

quizartinib · FLT3

13 (13-week rat, dog and monkey)

Vanrafia

atrasentan · Endothelin A receptor

39 (9-month dog)

Veklury

remdesivir · SARS-CoV-2 RNA polymerase

4 (4-week rat and monkey)

Velsipity

etrasimod · S1P1/S1P4/S1P5 receptors

39 (9-month dog)

Veozah

fezolinetant · Neurokinin-3 receptor

39 (39-week monkey)

Veppanu

vepdegestrant · Estrogen receptor (PROTAC degrader)

39 (9-month dog)

Verquvo

vericiguat · Soluble guanylate cyclase

39 (39-week dog)

Vivjoa

oteseconazole · Fungal CYP51

39 (9-month dog)

Vizz

aceclidine · Muscarinic agonist (miotic)

26 (6-month rabbit ocular)

Vonjo

pacritinib · JAK2/FLT3

39 (39-week dog)

Voquezna

vonoprazan · H+/K+-ATPase (potassium-competitive)

39 (39-week dog)

Voranigo

vorasidenib · IDH1/IDH2

13 (13-week rat and monkey)

Voydeya

danicopan · Complement factor D

39 (39-week dog)

Vtama

tapinarof · Aryl hydrocarbon receptor

39 (9-month minipig)

Vyndaqel

tafamidis · Transthyretin (stabiliser)

39 (39-week dog)

Wakix

pitolisant · Histamine H3 receptor

39 (9-month monkey)

Wayrilz

rilzabrutinib · BTK (reversible covalent)

39 (9-month dog)

Welireg

belzutifan · HIF-2α

13 (3-month rat and dog)

Winlevi

clascoterone · Androgen receptor (topical)

39 (39-week dermal minipig)

Xacduro

sulbactam and durlobactam · PBPs; beta-lactamase (durlobactam)

4 (28-day dog)

Xcopri

cenobamate · Sodium channel / GABA-A

52 (52-week monkey)

Xdemvy

lotilaner · Mite GABA-Cl channel

39 (9-month dog ocular)

Xeglyze

abametapir · Lice metalloproteinases

4 (28-day minipig dermal)

Xenleta

lefamulin · Bacterial ribosome (50S PTC)

13 (13-week IV studies)

Xocova

ensitrelvir · SARS-CoV-2 3CL protease

4 (4-week rat and monkey)

Xolremdi

mavorixafor · CXCR4

39 (39-week dog)

Xpovio

selinexor · XPO1

13 (13-week rat and monkey)

Zavzpret

zavegepant · CGRP receptor

39 (39-week monkey)

Zaynich

cefepime and zidebactam · PBPs; beta-lactam enhancer (zidebactam)

13 (13-week dog)

Zegfrovy

sunvozertinib · EGFR exon 20 insertion

13 (13-week rat and dog)

Zenbexus

iberdomide · Cereblon (CELMoD)

39 (9-month cynomolgus monkey)

Zeposia

ozanimod · S1P1/S1P5 receptor

39 (39-week monkey)

Zepzelca

lurbinectedin · DNA minor groove (transcription)

24 (8-cycle q3w rat and monkey)

Zevtera

ceftobiprole medocaril · Penicillin-binding proteins

13 (13-week rat, marmoset and dog)

Zokinvy

lonafarnib · Farnesyltransferase

52 (1-year monkey)

Ztalmy

ganaxolone · GABA-A receptor (positive modulator)

52 (12-month dog)

Zulresso

brexanolone · GABA-A receptor (positive modulator)

4 weeks

Zurzuvae

zuranolone · GABA-A receptor (positive modulator)

39 (9-month dog)

Zycubo

copper histidinate · Copper replacement (Menkes disease)

13 (13-week juvenile rat)

Summary across all 211 small molecules →