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Precedia/Small molecules/Lytgobi/First dose

Lytgobi: how was the first human dose set?

futibatinib · FGFR1-4 (covalent)
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 Lytgobi 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: Increased plasma phosphorus, ectopic mineralization in multiple tissues and bone lesions at clinically relevant exposures (FDA multi-discipline review, p. 42)

Full method, every step sourced →

NOAEL / key findings
Increased plasma phosphorus, ectopic mineralization in multiple tissues and bone lesions at clinically relevant exposures
“Drug‐related findings in both species were consistent with FGFR inhibition including increases in plasma phosphorus, ectopic mineralization in multiple tissues, and lesions in bone at exposure levels that are in range with human exposures at the recommended clinical dose of 20 mg.”
✓ VerifiedFDA multi-discipline review, p. 42Source ↗

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Krazati

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Leqselvi

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Myqorzo

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Nexletol

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Nextstellis

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Nourianz

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Nubeqa

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Ogsiveo

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Ohtuvayre

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Ojemda

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Ojjaara

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Olinvyk

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Not stated in public reviews

Omlonti

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Not stated in public reviews

Ongentys

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Not stated in public reviews

Orgovyx

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Orladeyo

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Not stated in public reviews

Orlynvah

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

Orserdu

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Not stated in public reviews

Orzeyful

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Oxbryta

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Palsonify

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Paxlovid

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Not stated in public reviews

Pemazyre

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Piqray

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Not stated in public reviews

Ponvory

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Not stated in public reviews

Pretomanid

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Not stated in public reviews

Pyrukynd

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Qelbree

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Qulipta

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Quviviq

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Rapiblyk

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Not stated in public reviews

Revuforj

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Not stated in public reviews

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Simtriyo

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Skyclarys

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Not stated in public reviews

Sohonos

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Not stated in public reviews

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Not stated in public reviews

Sunlenca

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Not stated in public reviews

Sunosi

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Tabrecta

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Tepmetko

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Trikafta

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Verquvo

vericiguat · Soluble guanylate cyclase
Not stated in public reviews

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Not stated in public reviews

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Vonjo

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Not stated in public reviews

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Not stated in public reviews

Voranigo

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Vtama

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Vyndaqel

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belzutifan · HIF-2α
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Not stated in public reviews

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Not stated in public reviews

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Not stated in public reviews

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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

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Not stated in public reviews

Summary across all 211 small molecules →