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Precedia/Small molecules/Inqovi/First dose

Inqovi: how was the first human dose set?

decitabine and cedazuridine · DNMT (decitabine); cytidine deaminase (cedazuridine)
Check my plan vs. these
First-in-human starting dose
Not stated in public reviews
Why it's blank

The public FDA and EMA reviews of Inqovi don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.

How it's usually set for oncology small molecules (ICH S9)

HNSTD/STD10 is the method used for anticancer drugs in patients: the start dose is one-sixth of the highest non-severely toxic dose (HNSTD) in non-rodents, or one-tenth of the dose severely toxic to 10% of rodents (STD10), scaled by body surface area. The aim is a dose that is pharmacologically active yet reasonably safe.

“A common approach for many small molecules is to set a start dose at 1/10 the Severely Toxic Dose in 10% of the animals (STD 10) in rodents. If the non-rodent is the most appropriate species, then 1/6 the Highest Non-Severely Toxic Dose (HNSTD) is considered an appropriate starting dose.”
✓ VerifiedICH 2009: ICH S9: Nonclinical Evaluation for Anticancer Pharmaceuticals, p. 13Source ↗
This product's starting point

NOAEL / key findings: Reversible myelosuppression; reversible reproductive tract effects from cedazuridine (FDA multi-discipline review, p. 61)

Full method, every step sourced →

NOAEL / key findings
Reversible myelosuppression; reversible reproductive tract effects from cedazuridine
“In summary, the main repeat-dose toxicity findings from studies conducted in mice, rats, and monkeys were characterized by reversible myelosuppression (leukopenia, neutropenia, lymphopenia, and/or decreased platelet counts) due to decitabine, or both (ASTX727), reversible reproductive tract effects due to cedazuridine”
✓ VerifiedFDA multi-discipline review, p. 61Source ↗

Email me this as a cited memo

First dose for Inqovi, each with the regulator's own words, the page and a link. Ready to paste into a briefing document or send to your team.

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Crenessity

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Cypsedo

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Daybue

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Dayvigo

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Not stated in public reviews

Defencath

taurolidine and heparin · Antimicrobial catheter lock
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Dojolvi

triheptanoin · Anaplerotic energy substrate
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Duvyzat

givinostat · Histone deacetylase (class I/II)
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Egaten

triclabendazole · Fasciola (tubulin)
Not stated in public reviews

Ekterly

sebetralstat · Plasma kallikrein
Not stated in public reviews

Ensacove

ensartinib · ALK
Not stated in public reviews

Evrysdi

risdiplam · SMN2 splicing
Not stated in public reviews

Exblifep

cefepime and enmetazobactam · PBPs; beta-lactamase (enmetazobactam)
Not stated in public reviews

Exkivity

mobocertinib · EGFR exon 20 insertion
Not stated in public reviews

Exxua

gepirone · 5-HT1A receptor
Not stated in public reviews

Fabhalta

iptacopan · Complement factor B
Not stated in public reviews

Fetroja

cefiderocol · Penicillin-binding proteins
Not stated in public reviews

Fexinidazole

fexinidazole · Trypanosoma brucei
Not stated in public reviews

Filspari

sparsentan · Endothelin A / angiotensin II receptors
Not stated in public reviews

Fotivda

tivozanib · VEGFR1-3
Not stated in public reviews

Foundayo

orforglipron · GLP-1 receptor (non-peptide)
Not stated in public reviews

Fruzaqla

fruquintinib · VEGFR1-3
Not stated in public reviews

Gavreto

pralsetinib · RET
Not stated in public reviews

Gemtesa

vibegron · β3-adrenergic receptor
Not stated in public reviews

Gomekli

mirdametinib · MEK1/2
Not stated in public reviews

Grafapex

treosulfan · DNA alkylation
Not stated in public reviews

Hernexeos

zongertinib · HER2 (mutant)
Not stated in public reviews

Hyrnuo

sevabertinib · HER2 (mutant)
Not stated in public reviews

Ibsrela

tenapanor · NHE3
Not stated in public reviews

Ibtrozi

taletrectinib · ROS1
Not stated in public reviews

Idvynso

doravirine and islatravir · NNRTI; NRTTI
Not stated in public reviews

Inluriyo

imlunestrant · Estrogen receptor (SERD)
Not stated in public reviews

Inpefa

sotagliflozin · SGLT1/SGLT2
Not stated in public reviews

Inrebic

fedratinib · JAK2
Not stated in public reviews

Iqirvo

elafibranor · PPARα/δ
Not stated in public reviews

Isturisa

osilodrostat · 11β-hydroxylase (CYP11B1)
Not stated in public reviews

Itovebi

inavolisib · PI3Kα (mutant-selective)
Not stated in public reviews

Jascayd

nerandomilast · PDE4B
Not stated in public reviews

Jaypirca

pirtobrutinib · BTK (non-covalent)
Not stated in public reviews

Jesduvroq

daprodustat · HIF prolyl hydroxylase
Not stated in public reviews

Jideytro

zidesamtinib · ROS1
Not stated in public reviews

Joenja

leniolisib · PI3Kδ
Not stated in public reviews

Journavx

suzetrigine · NaV1.8
Not stated in public reviews

Kerendia

finerenone · Mineralocorticoid receptor
Not stated in public reviews

Klisyri

tirbanibulin · Tubulin / Src
Not stated in public reviews

Komzifti

ziftomenib · Menin-KMT2A
Not stated in public reviews

Koselugo

selumetinib · MEK1/2
Not stated in public reviews

Krazati

adagrasib · KRAS G12C
Not stated in public reviews

Kygevvi

doxecitine and doxribtimine · Pyrimidine nucleoside replacement (TK2 deficiency)
Not stated in public reviews

Lampit

nifurtimox · Trypanosoma cruzi
Not stated in public reviews

Lazcluze

lazertinib · EGFR (mutant-selective)
Not stated in public reviews

Leqselvi

deuruxolitinib · JAK1/JAK2
Not stated in public reviews

Lifyorli

relacorilant · Glucocorticoid receptor (antagonist)
Not stated in public reviews

Litfulo

ritlecitinib · JAK3/TEC kinases
Not stated in public reviews

Livdelzi

seladelpar · PPARδ
Not stated in public reviews

Livmarli

maralixibat · IBAT (ASBT)
Not stated in public reviews

Livtencity

maribavir · CMV UL97 protein kinase
Not stated in public reviews

Lupkynis

voclosporin · Calcineurin
Not stated in public reviews

Lybalvi

olanzapine and samidorphan · D2/5-HT2A; opioid receptors (samidorphan)
Not stated in public reviews

Lynavoy

linerixibat · IBAT
Not stated in public reviews

Lynkuet

elinzanetant · NK1/NK3 receptors
Not stated in public reviews

Lytgobi

futibatinib · FGFR1-4 (covalent)
Not stated in public reviews

Mayzent

siponimod · S1P1/S1P5 receptor
Not stated in public reviews

Miebo

perfluorohexyloctane · Tear film evaporation barrier
Not stated in public reviews

Miplyffa

arimoclomol · Heat-shock response amplifier
Not stated in public reviews

Modeyso

dordaviprone · DRD2 antagonist / ClpP agonist
Not stated in public reviews

Myqorzo

aficamten · Cardiac myosin
Not stated in public reviews

Nereus

tradipitant · NK1 receptor
Not stated in public reviews

Nexletol

bempedoic acid · ATP citrate lyase
Not stated in public reviews

Nextstellis

drospirenone and estetrol · Estrogen / progestin receptors
Not stated in public reviews

Nourianz

istradefylline · Adenosine A2A receptor
Not stated in public reviews

Nubeqa

darolutamide · Androgen receptor
Not stated in public reviews

Nurtec ODT

rimegepant · CGRP receptor
Not stated in public reviews

Nuzolvence

zoliflodacin · Bacterial topoisomerase II
Not stated in public reviews

Ogsiveo

nirogacestat · Gamma secretase
Not stated in public reviews

Ohtuvayre

ensifentrine · PDE3/PDE4
Not stated in public reviews

Ojemda

tovorafenib · RAF (type II pan-RAF)
Not stated in public reviews

Ojjaara

momelotinib · JAK1/JAK2/ACVR1
Not stated in public reviews

Olinvyk

oliceridine · μ-opioid receptor (G-protein biased)
Not stated in public reviews

Omlonti

omidenepag isopropyl · EP2 receptor
Not stated in public reviews

Ongentys

opicapone · COMT
Not stated in public reviews

Orgovyx

relugolix · GnRH receptor
Not stated in public reviews

Orladeyo

berotralstat · Plasma kallikrein
Not stated in public reviews

Orlynvah

sulopenem etzadroxil and probenecid · Penicillin-binding proteins
Not stated in public reviews

Orserdu

elacestrant · Estrogen receptor (SERD)
Not stated in public reviews

Orzeyful

oveporexton · Orexin OX2 receptor agonist
Not stated in public reviews

Oxbryta

voxelotor · HbS polymerisation
Not stated in public reviews

Palsonify

paltusotine · Somatostatin receptor 2
Not stated in public reviews

Paxlovid

nirmatrelvir and ritonavir · SARS-CoV-2 Mpro (3CL protease)
Not stated in public reviews

Pemazyre

pemigatinib · FGFR1-3
Not stated in public reviews

Piqray

alpelisib · PI3Kα
Not stated in public reviews

Pizensy

lactitol · Osmotic laxative
Not stated in public reviews

Ponvory

ponesimod · S1P1 receptor
Not stated in public reviews

Pretomanid

pretomanid · Mycobacterial cell wall / respiration
Not stated in public reviews

Pyrukynd

mitapivat · Pyruvate kinase (activator)
Not stated in public reviews

Qelbree

viloxazine · Norepinephrine reuptake
Not stated in public reviews

Qinlock

ripretinib · KIT/PDGFRA
Not stated in public reviews

Qulipta

atogepant · CGRP receptor
Not stated in public reviews

Quviviq

daridorexant · Orexin OX1/OX2 receptors
Not stated in public reviews

Rapiblyk

landiolol · β1-adrenergic receptor
Not stated in public reviews

Rasonque

daraxonrasib · RAS(ON) multi-selective
Not stated in public reviews

Recarbrio

imipenem, cilastatin and relebactam · Beta-lactamase (relebactam)
Not stated in public reviews

Relyvrio

sodium phenylbutyrate and taurursodiol · ER stress / mitochondrial (proposed)
Not stated in public reviews

Retevmo

selpercatinib · RET
Not stated in public reviews

Revtorpyk

gedatolisib · PI3K/mTOR
Not stated in public reviews

Revuforj

revumenib · Menin-KMT2A
Not stated in public reviews

Reyvow

lasmiditan · 5-HT1F receptor
Not stated in public reviews

Rezdiffra

resmetirom · Thyroid hormone receptor β
Not stated in public reviews

Rezlidhia

olutasidenib · IDH1 (mutant)
Not stated in public reviews

Rezurock

belumosudil · ROCK2
Not stated in public reviews

Rezzayo

rezafungin · Fungal glucan synthase
Not stated in public reviews

Rhapsido

remibrutinib · BTK
Not stated in public reviews

Rinvoq

upadacitinib · JAK1
Not stated in public reviews

Romvimza

vimseltinib · CSF1R
Not stated in public reviews

Rozlytrek

entrectinib · TRK/ROS1/ALK
Not stated in public reviews

Rukobia

fostemsavir · HIV-1 gp120 (attachment)
Not stated in public reviews

Sephience

sepiapterin · Tetrahydrobiopterin precursor
Not stated in public reviews

Simtriyo

centanafadine · Triple monoamine reuptake
Not stated in public reviews

Skyclarys

omaveloxolone · Nrf2 activator
Not stated in public reviews

Sofdra

sofpironium · Muscarinic receptors (topical)
Not stated in public reviews

Sohonos

palovarotene · RARγ
Not stated in public reviews

Sotyktu

deucravacitinib · TYK2
Not stated in public reviews

Sunlenca

lenacapavir · HIV-1 capsid
Not stated in public reviews

Sunosi

solriamfetol · Dopamine/norepinephrine reuptake
Not stated in public reviews

Tabrecta

capmatinib · MET
Not stated in public reviews

Tavneos

avacopan · C5a receptor (C5aR1)
Not stated in public reviews

Tazverik

tazemetostat · EZH2
Not stated in public reviews

Tepmetko

tepotinib · MET
Not stated in public reviews

Trikafta

elexacaftor, tezacaftor and ivacaftor · CFTR
Not stated in public reviews

Truqap

capivasertib · AKT1-3
Not stated in public reviews

Truseltiq

infigratinib · FGFR1-3
Not stated in public reviews

Tryptyr

acoltremon · TRPM8 agonist
Not stated in public reviews

Tryvio

aprocitentan · Endothelin A/B receptors
Not stated in public reviews

Tukysa

tucatinib · HER2
Not stated in public reviews

Turalio

pexidartinib · CSF1R
Not stated in public reviews

Ubrelvy

ubrogepant · CGRP receptor
Not stated in public reviews

Ukoniq

umbralisib · PI3Kδ / CK1ε
Not stated in public reviews

Utebzi

tebipenem pivoxil · Penicillin-binding proteins
Not stated in public reviews

Vafseo

vadadustat · HIF prolyl hydroxylase
Not stated in public reviews

Vanflyta

quizartinib · FLT3
Not stated in public reviews

Veklury

remdesivir · SARS-CoV-2 RNA polymerase
Not stated in public reviews

Velsipity

etrasimod · S1P1/S1P4/S1P5 receptors
Not stated in public reviews

Veozah

fezolinetant · Neurokinin-3 receptor
Not stated in public reviews

Veppanu

vepdegestrant · Estrogen receptor (PROTAC degrader)
Not stated in public reviews

Verquvo

vericiguat · Soluble guanylate cyclase
Not stated in public reviews

Vivjoa

oteseconazole · Fungal CYP51
Not stated in public reviews

Vizz

aceclidine · Muscarinic agonist (miotic)
Not stated in public reviews

Vonjo

pacritinib · JAK2/FLT3
Not stated in public reviews

Voquezna

vonoprazan · H+/K+-ATPase (potassium-competitive)
Not stated in public reviews

Voranigo

vorasidenib · IDH1/IDH2
Not stated in public reviews

Voydeya

danicopan · Complement factor D
Not stated in public reviews

Vtama

tapinarof · Aryl hydrocarbon receptor
Not stated in public reviews

Vyndaqel

tafamidis · Transthyretin (stabiliser)
Not stated in public reviews

Wakix

pitolisant · Histamine H3 receptor
Not stated in public reviews

Wayrilz

rilzabrutinib · BTK (reversible covalent)
Not stated in public reviews

Welireg

belzutifan · HIF-2α
Not stated in public reviews

Winlevi

clascoterone · Androgen receptor (topical)
Not stated in public reviews

Xacduro

sulbactam and durlobactam · PBPs; beta-lactamase (durlobactam)
Not stated in public reviews

Xcopri

cenobamate · Sodium channel / GABA-A
Not stated in public reviews

Xdemvy

lotilaner · Mite GABA-Cl channel
Not stated in public reviews

Xeglyze

abametapir · Lice metalloproteinases
Not stated in public reviews

Xenleta

lefamulin · Bacterial ribosome (50S PTC)
Not stated in public reviews

Xocova

ensitrelvir · SARS-CoV-2 3CL protease
Not stated in public reviews

Xolremdi

mavorixafor · CXCR4
Not stated in public reviews

Zavzpret

zavegepant · CGRP receptor
Not stated in public reviews

Zaynich

cefepime and zidebactam · PBPs; beta-lactam enhancer (zidebactam)
Not stated in public reviews

Zegfrovy

sunvozertinib · EGFR exon 20 insertion
Not stated in public reviews

Zenbexus

iberdomide · Cereblon (CELMoD)
Not stated in public reviews

Zeposia

ozanimod · S1P1/S1P5 receptor
Not stated in public reviews

Zepzelca

lurbinectedin · DNA minor groove (transcription)
Not stated in public reviews

Zevtera

ceftobiprole medocaril · Penicillin-binding proteins
Not stated in public reviews

Zokinvy

lonafarnib · Farnesyltransferase
Not stated in public reviews

Ztalmy

ganaxolone · GABA-A receptor (positive modulator)
Not stated in public reviews

Zulresso

brexanolone · GABA-A receptor (positive modulator)
Not stated in public reviews

Zurzuvae

zuranolone · GABA-A receptor (positive modulator)
Not stated in public reviews

Zycubo

copper histidinate · Copper replacement (Menkes disease)
Not stated in public reviews

Summary across all 211 small molecules →