Adbry
tralokinumab
Species
Monkey
Longest study
26 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Cynomolgus monkey only
“Therefore, cynomolgus monkey was selected as a single pharmacologically relevant species for use in nonclinical studies with tralokinumab.”
Why that species
95% IL-13 sequence homology with cynomolgus monkey versus 55-62% in rodents; no mouse cross-reactivity
“The IL-13 amino acid sequence homology between human and cynomolgus monkey is 95%, whereas that between human and rodent is 55% for mouse and 62% for rat. Tralokinumab did not cross-react with mouse IL-13.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkey
“Therefore, cynomolgus monkey was selected as a single pharmacologically relevant species for use in nonclinical studies with tralokinumab.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“The no observed adverse effect level (NOAEL) for tralokinumab in cynomolgus monkeys was 90 mg/kg/week in the 13-week SC toxicology study and 100 mg/kg/week in the 26-week IV toxicology study.”
Pivotal GLP studies
Cynomolgus monkey 4-, 13- and 26-week weekly IV studies; 4- and 13-week weekly SC studies
“The repeat dose toxicity studies included 4-, 13- and 26-weeks studies with weekly IV dosing at levels up to 100 mg/kg and weekly SC injections of up to 350 mg/injection for 4- and 13-weeks.”
Route in tox
IV and SC
“Three IV and two SC repeat-dose toxicity studies were submitted.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genotoxicity No studies have been performed in accordance with ICH S6(R1).”
Carcinogenicity
Not conducted; weight-of-evidence assessment found no concern for increased carcinogenic risk
“In line with ICH S6 (R1), a weight of evidence approach has been provided which suggests that there are no identified concerns for increased carcinogenic risk with the use of tralokinumab.”
Reproductive & developmental
Monkey fertility, EFD, PPND and ePPND studies; ePPND: no embryofetal toxicity, malformations or infant developmental effects to 6 months
“No treatment-related adverse effects on embryofetal toxicity or malformations, or on morphological, functional, or immunological development were observed in the infants from birth to 6 months of age.”
Safety pharmacology
Incorporated into repeat-dose monkey studies; no cardiovascular, respiratory or behavioral effects up to 100 mg/kg/week
“Repeated administration of tralokinumab up to 100 mg/kg/week had no adverse effects on the evaluated parameters for cardiovascular, respiratory, and behavioral effects.”
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 Adbry 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 monoclonal antibodies 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: NOAEL 90 mg/kg/week (13-week SC) and 100 mg/kg/week (26-week IV); no adverse effects or target organs (FDA integrated review, p. 131)
NOAEL / key findings
NOAEL 90 mg/kg/week (13-week SC) and 100 mg/kg/week (26-week IV); no adverse effects or target organs
“The no observed adverse effect level (NOAEL) for tralokinumab in cynomolgus monkeys was 90 mg/kg/week in the 13-week SC toxicology study and 100 mg/kg/week in the 26-week IV toxicology study.”
Risksopen answer page →
Immune & cytokine safety
No significant modulation of CD4/CD8 T cells, NK cells or mature B cells in 26-week monkey study
“In addition, the 26-week study included an immunophenotyping assessment which indicated that tralokinumab did not significantly modulate any of the immune cell populations investigated which including CD4 and CD8 T cells, NK cells and mature B cells.”
Biodistribution & persistence
Placental transfer in monkeys, neonate serum levels comparable to or above maternal
“There was clear evidence of placental transfer in both studies with neonate serum levels measured comparable or even in excess of maternal levels.”
Modality-specific risk
Low circulating IL-13 in naive monkeys may mask pharmacological effects, limiting predictivity
“Whilst there were no apparent tralokinumab related effects in these studies, this could be explained by very low circulating IL-13 levels in naïve monkeys.”