Kerendia
finerenone
Species
RatDog
Longest study
39 wk
Genotox
Conducted Conducted
Carcinogenicity
Conducted Conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Rat and dog
“Even so, general toxicity studies using oral gavage exposure are available for mouse, rat and dog, where rat and dog are considered main general toxicology species and have been used for studies of up to 26- and 39-weeks duration respectively.”
Why that species
Pharmacologically relevant based on receptor binding and metabolite formation
“Both species are considered pharmacologically relevant based on appropriate binding data and formation of metabolites.”
Surrogate molecule
No surrogate; the clinical compound was tested
“The oral route (oral gavage) has been used throughout the study programme, as this route is the intended clinical route.”
Study lengthopen answer page →
Longest pivotal study
39 (9-month dog)
“Even so, general toxicity studies using oral gavage exposure are available for mouse, rat and dog, where rat and dog are considered main general toxicology species and have been used for studies of up to 26- and 39-weeks duration respectively.”
Pivotal GLP studies
26-week rat and 39-week dog oral gavage studies
“Even so, general toxicity studies using oral gavage exposure are available for mouse, rat and dog, where rat and dog are considered main general toxicology species and have been used for studies of up to 26- and 39-weeks duration respectively.”
Route in tox
Oral gavage
“The oral route (oral gavage) has been used throughout the study programme, as this route is the intended clinical route.”
Skipped studiesopen answer page →
Genotoxicity
Negative in Ames, in vitro chromosomal aberration and in vivo mouse micronucleus assays
“Finerenone was also negative in the in vitro chromosomal aberration assay in mammalian cells and in the in vivo mouse micronucleus test.”
Carcinogenicity
2-year mouse and rat: no significant increase in neoplasms
“Two-year carcinogenicity studies conducted in mice and rats showed no significant increase in neoplasms in males or females in either study; the CDER Exec CAC concurred with this conclusion.”
Reproductive & developmental
Rat EFD: reduced fetal weight and retarded ossification at maternally toxic 10 mg/kg/day (19x unbound AUC)
“In the embryo-fetal toxicity study in rats, finerenone resulted in reduced placental weights and signs of fetal toxicity, including reduced fetal weights and retarded ossification at the maternal toxic dose of 10 mg/kg/day, corresponding to an AUC unbound of 19 times that in humans.”
Safety pharmacology
No adverse CNS, respiratory, hemodynamic/ECG or hERG effects
“Finerenone showed no adverse effects on CNS parameters and respiratory functions (rat), on hemodynamic/ECG parameters (dog), and on cardiac repolarization in vitro (hERG K+ current).”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Kerendia 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 small molecules outside oncology
Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.
“In general, one should consider using a safety factor of at least 10. The MRSD should be obtained by dividing the HED by the safety factor.”
This product's starting point
NOAEL / key findings: Exaggerated pharmacology: adrenals (rat, dog) and reduced prostate size (dog) (FDA integrated review, p. 58)
NOAEL / key findings
Exaggerated pharmacology: adrenals (rat, dog) and reduced prostate size (dog)
“Target organs of exaggerated pharmacology after chronic treatment were the adrenals in both the rat and dog and also the prostate in the dog (decrease in prostate size and weight not accompanied by histopathological changes).”
Risksopen answer page →
Immune & cytokine safety
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Biodistribution & persistence
No specific affinity for melanin-bearing tissues (eye, skin) in pigmented rats
“Similar results were obtained in pigmented Long Evans rats and there was no indication of any specific affinity of substance-associated radioactivity to melanin bearing tissues such as eye wall or skin.”
Modality-specific risk
Disproportionate human metabolite M-1 (qualified in 9-month dog study)
“In the dog 9-month study, the disproportionate human metabolite M-1 was qualified.”