Removab
catumaxomab
Sources:EMA assessment report ↗
Species
no relevantMonkeyMouse
Longest study
none
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
No relevant species; in vitro human cells plus mouse surrogate (BiLu); limited single-dose rodent/monkey
“A number of common laboratory animal species, including the three monkeys marmoset (Callitrix sp.), cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) were tested histologically for catumaxomab binding, but none showed a binding pattern similar to that of human tissues, and were consequently considered non-relevant.”
Why that species
Binding essentially human-specific; no animal species showed human-like tissue binding
“The non-clinical programme was adapted to the fact that catumaxomab is a protein, and its binding properties are essentially specific for humans.”
Surrogate molecule
Yes: BiLu (anti-human EpCAM x anti-mouse CD3) used for pharmacology, PK and toxicology in mice
“A surrogate antibody (BiLu), which is of equivalent structure to catumaxomab and has the same principal target specificity but binds to mouse CD3 instead of human CD3, was used for pharmacology, pharmacokinetic and toxicology studies in mouse models.”
Study lengthopen answer page →
Longest pivotal study
0 (no in vivo tox study)
“Repeat-dose toxicity studies have not been submitted.”
Pivotal GLP studies
No repeat-dose studies; single-dose catumaxomab in mice, rats, one cynomolgus; BiLu single-dose mouse; rabbit local tolerance
“In the few studies performed in rats, mice and one cynomolgus monkey, no acute toxicity was seen even at very high doses of catumaxomab.”
Route in tox
IV (single-dose, escalating monkey infusion); i.p. and other routes in rabbit local tolerance
“Administration of 150 µg i.p. catumaxomab showed an histopathological moderate subchronic inflammation of skin and abdominal muscle after administration of the test item in one animal.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (not submitted; biologic, no relevant model)
“Genotoxicity studies have not been submitted.”
Carcinogenicity
Not conducted (not submitted)
“Carcinogenicity studies have not been submitted.”
Reproductive & developmental
Not conducted (not submitted)
“Reproductive and developmental toxicity studies have not been submitted.”
Safety pharmacology
No in vivo studies; human tissue cross-reactivity and in vitro hepatocyte studies
“The safety pharmacology programme was defined by the accessibility of intact monoclonal antibodies in vivo to EpCAM positive tissue.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL for catumaxomab; no acute toxicity at high single doses; surrogate BiLu suggested liver toxicity
“The single-dose toxicity studies with BiLu indicate that catumaxomab may cause liver toxicity.”
Risksopen answer page →
Immune & cytokine safety
In vitro TNF-α, IL-6, IL-2 release (needs EpCAM+ cells); no cytokine change in monkey; anti-mouse/rat ADA
“The greatest stimulatory effect of catumaxomab was seen for TNF-α and IL-6, and a smaller stimulatory effect was seen for IL-2.”
Biodistribution & persistence
123I-catumaxomab localised to EpCAM+ xenograft; non-target organ kinetics like control antibody; complete i.p. bioavailability (BiLu)
“Catumaxomab localised to the tumour. The time-activity course for both catumaxomab and a control antibody without tumour specificity in non-target organs was similar.”
Modality-specific risk
No relevant model: T-cell engager cytokine release, hepatotoxicity and murine-protein immunogenicity left to clinic
“As argued by the applicant, the toxicity findings obtained with the surrogate antibody BiLu were considered of limited value. Due to the lack of a relevant animal model, safety assessment of catumaxomab mainly depend on the clinical safety assessment.”