Poteligeo
mogamulizumab
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
“Toxicology studies were only conducted in cynomolgus monkeys due to the limited cross reactivity profile of mogamulizumab.”
Why that species
Binds lymphocytes only from humans and cynomolgus monkeys (identical CCR4 epitope sequence); no binding in dog, rat, mouse
“Biotinylated mogamulizumab specifically bound peripheral lymphocytes from humans and cynomolgus monkeys only; most the specific binding was in the CD4-positive subset. Similar binding in humans and cynomolgus monkeys is expected given the CCR4 amino acid sequence at the mogamulizumab binding region is identical in humans and cynomolgus monkeys.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys
“Toxicology studies were only conducted in cynomolgus monkeys due to the limited cross reactivity profile of mogamulizumab.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“Dose and frequency of dosing: 0, 2.5, 10, or 40 mg/kg; test article was administered once weekly for 26 weeks”
Pivotal GLP studies
GLP cynomolgus monkey 26-week once-weekly IV study (2.5, 10, 40 mg/kg), plus 4-week study
“In the 26-week study, mogamulizumab was administered IV at doses of 2.5, 10, or 40 mg/kg once weekly. Mogamulizumab was well-tolerated, and no adverse mogamulizumab-related changes were observed.”
Route in tox
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Not conducted per ICH S6(R1).”
Carcinogenicity
Not conducted (ICH S6(R1), S1, S9; advanced cancer)
“Not conducted per ICH S6(R1), S1, and S9.”
Reproductive & developmental
Monkey EFD (organogenesis through delivery): no embryo-fetal lethality, teratogenicity or fetal growth retardation
“administration of mogamulizumab to pregnant cynomolgus monkeys from the start of organogenesis through delivery did not show a potential for embryo-foetal lethality, teratogenicity, or foetal growth retardation.”
Safety pharmacology
Incorporated into repeat-dose monkey studies; no cardiovascular, respiratory, renal or CNS effects
“Safety pharmacology endpoints were incorporated into the repeat-dose toxicity studies, and there was no evidence of mogamulizumab-related effects on the cardiovascular, respiratory, renal, or central nervous systems.”
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 Poteligeo 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 monoclonal antibodies (ICH S9)
In cancer patients the start dose should be pharmacologically active yet reasonably safe. A common small-molecule approach is one-tenth of the dose severely toxic to 10% of rodents, or one-sixth of the highest non-severely toxic dose in non-rodents.
“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.”
This product's starting point
NOAEL / key findings: Monkey NOAEL ≥40 mg/kg (highest dose); no toxicologically significant changes (EMA assessment report, p. 47)
NOAEL / key findings
Monkey NOAEL ≥40 mg/kg (highest dose); no toxicologically significant changes
“The NOAEL of mogamulizumab was judged to be 40 mg/kg or greater since no toxicologically significant changes were observed in any examination.”
Risksopen answer page →
Immune & cytokine safety
In vitro cytokine release (IL-6, TNF-α, IFN-γ) varied by assay format, greatest in solid-phase PBMC assays
“Results of the cytokine release assays varied by the experimental conditions; mogamulizumab generally caused greater cytokine release (IL-6, TNF-α, and IFN-γ) in solid phase assays with isolated PBMCs.”
Biodistribution & persistence
Placental transfer: fetal plasma exposure ~60% of maternal in monkeys
“At the end of the study plasma exposure of mogamulizumab in the fetuses was ~60% that observed in the dams; this finding is consistent with the expected transfer of mogamulizumab across the placental barrier.”
Modality-specific risk
Dermatologic adverse events in patients not predicted by monkey repeat-dose studies
“Dermatologic adverse events (AE) were observed in humans that were not predicted by the repeat-dose toxicity studies in cynomolgus monkeys.”