Livdelzi
seladelpar
Species
MonkeyRatMouseDog
Longest study
52 wk
Genotox
Conducted Conducted
Carcinogenicity
Conducted Conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Rat and cynomolgus monkey (also mouse and dog)
“Repeat-dose po administration of seladelpar was evaluated at up to 13 weeks in CD-1 mice, up to 26 weeks in Sprague-Dawley rats, up to 4 weeks in dogs, and up to 52 weeks in cynomolgus monkeys.”
Why that species
Multiple species chosen because PPAR sensitivity differs between species
“The selection of multiple species for the non-clinical programme was justified by the sensitivity differences towards PPARs between species.”
Surrogate molecule
No surrogate; the clinical compound was tested
“General toxicology studies with seladelpar (orally administered) were performed in mice, rats, dogs, and monkeys, with adverse effects noted in each species.”
Study lengthopen answer page →
Longest pivotal study
52 (52-week monkey)
“Repeat-dose po administration of seladelpar was evaluated at up to 13 weeks in CD-1 mice, up to 26 weeks in Sprague-Dawley rats, up to 4 weeks in dogs, and up to 52 weeks in cynomolgus monkeys.”
Pivotal GLP studies
Oral studies up to 26 weeks in rats and 52 weeks in cynomolgus monkeys (13-week mouse, 4-week dog)
“Repeat-dose po administration of seladelpar was evaluated at up to 13 weeks in CD-1 mice, up to 26 weeks in Sprague-Dawley rats, up to 4 weeks in dogs, and up to 52 weeks in cynomolgus monkeys.”
Route in tox
Oral
“General toxicology studies with seladelpar (orally administered) were performed in mice, rats, dogs, and monkeys, with adverse effects noted in each species.”
Skipped studiesopen answer page →
Genotoxicity
Negative in Ames, mouse lymphoma and in vivo mouse micronucleus assays
“Genetic toxicology studies showed that seladelpar was negative in the in vitro bacterial reverse mutation (Ames) assay, the in vitro mouse lymphoma assay, and the in vivo mouse micronucleus test.”
Carcinogenicity
2-year mouse: hepatocellular adenoma or carcinoma at 6x (males) and 140x (females) human AUC
“In a 2-year study in mice, oral administration of seladelpar produced hepatocellular adenoma or carcinoma at 6 times the human exposure (AUC at the recommended dose) in males and at 140 times the human exposure in females.”
Reproductive & developmental
No effects on male or female rat fertility (up to 271x and 115x human AUC)
“Seladelpar had no effects on fertility or reproductive function in male rats at up to 271 times the human exposure (AUC) at the recommended dose or in female rats at up to 115 times the human exposure.”
Safety pharmacology
No significant cardiovascular, respiratory or CNS concerns
“Overall, the safety pharmacology data indicates that there are no safety issues of significant concern for cardiovascular function, respiratory function, or the central nervous system.”
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 Livdelzi 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: Main target organs: liver, skeletal and cardiac muscle, stomach and kidney (FDA integrated review, p. 93)
NOAEL / key findings
Main target organs: liver, skeletal and cardiac muscle, stomach and kidney
“The main target organs of toxicity were liver, skeletal and cardiac muscle, stomach, and kidney.”
Risksopen answer page →
Immune & cytokine safety
No immunotoxicity in repeat-dose studies; negative mouse local lymph node assay
“Seladelpar did not show potential for immunotoxicity in the repeat-dose toxicity studies and no sensitisation potential was recorded in the local lymph node assay in mouse.”
Biodistribution & persistence
Wide distribution in rats (QWBA), highest in liver, kidney and bladder
“Seladelpar was widely distributed in rats, as demonstrated by quantitative whole-body autoradiography (QWBA) data in both non-pigmented and pigmented rats with the highest radioactivity detected in the liver, kidney, and bladder.”
Modality-specific risk
Rodent liver effects and tumors; PPARα-dependent (rodent-specific) mode of action investigated
“The 14-day study in the PPARα null mice showed that wild-type mice are more sensitive to liver effects that PPARα null mice, suggesting that PPARα plays a role in the observed liver effects in mice.”