Bimzelx
bimekizumab
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
“The only relevant species for nonclinical testing is the nonhuman primate.”
Why that species
No or very low affinity for mouse IL-17A, IL-17F or IL-17AF; binds cynomolgus IL-17A/F
“The non-clinical evaluation has been conducted in the Cynomolgus monkey only since bimekizumab has no or very low affinity for mouse IL-17A, IL-17F or IL-17AF.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys (no anti-rodent IL-17A/F surrogate available)
“Bimekizumab is not pharmacologically active in rodents and no anti-rodent IL-17 A/F surrogate is available.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“The Applicant has conducted repeat dose toxicity studies in cynomolgus monkeys with weekly doses administered by subcutaneous injection for up to 26 weeks, followed by a treatment-free recovery period of up to 21 weeks”
Pivotal GLP studies
Cynomolgus monkey weekly SC repeat-dose studies up to 26 weeks with up to 21-week recovery
“The Applicant has conducted repeat dose toxicity studies in cynomolgus monkeys with weekly doses administered by subcutaneous injection for up to 26 weeks, followed by a treatment-free recovery period of up to 21 weeks”
Route in tox
Subcutaneous and intravenous
“Intravenous and subcutaneous routes of administration were explored.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“No genotoxicity studies have been conducted with bimekizumab in line with ICH S6 (R1) guideline.”
Carcinogenicity
Not conducted; literature weight-of-evidence shows no clear carcinogenicity concern from IL-17A/F inhibition
“In conclusion, the literature does not suggest a clear concern that inhibition of IL-17A and IL-17F would lead to carcinogenicity or tumor development.”
Reproductive & developmental
Monkey ePPND: NOAEL 50 mg/kg/week for maternal and developmental toxicity (38x MRHD)
“The no observed adverse effect level (NOAEL) for both maternal and developmental toxicity was identified as 50 mg/kg/week which is 38 times (based on mg/kg comparison) the maximum recommended human dose”
Safety pharmacology
Incorporated into monkey repeat-dose studies; no CNS, respiratory, ECG or blood pressure effects up to 200 mg/kg/week
“Clinical observations from the repeat-dose toxicity studies conducted in cynomolgus monkeys indicate bimekizumab does not induce central nervous system or respiratory effects. No ECG or blood pressure effects were observed in cynomolgus monkeys treated subcutaneously for 26 weeks with up to 200 mg/kg/week bimekizumab.”
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 Bimzelx 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 was highest dose in 8-week studies (200 and 20 mg/kg/week); none in 26-week study (skin findings, GI infection deaths) (EMA assessment report, p. 25)
NOAEL / key findings
NOAEL was highest dose in 8-week studies (200 and 20 mg/kg/week); none in 26-week study (skin findings, GI infection deaths)
“The no-observed adverse effect level (NOAEL) was the highest dose tested in the 8-week studies (200mg/kg/week and 20mg/kg/week, respectively, for Study NCD2260 and Study NCD2384). Due to the severity of skin findings in some high-dose animals and mortalities in the low dose group consecutive to GI infection, no NOAEL could be determined in the 26-week study.”
Risksopen answer page →
Immune & cytokine safety
Increased infection risk from reduced muco-epidermal immunity in single and repeat-dose monkey studies
“The main finding in single and repeat dose studies was the increased risk of infection due to reduced muco-epidermal immunity.”
Biodistribution & persistence
No cross-reactive binding in any human or cynomolgus monkey tissue
“No cross-reactive binding of bimekizumab conjugated to fluorescein isothiocyanate was observed in any human or monkey tissue at any concentration tested”
Modality-specific risk
Infections from exaggerated IL-17A/F pharmacology reducing muco-epidermal immunity
“Bimekizumab specifically inhibits IL-17A and IL-17F and as such muco-epidermal infections are considered to be related to exaggerated pharmacology, leading to decreased muco-epidermal immunity.”