Soliris
eculizumab
Species
Mouse
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
Mouse (surrogate antibody) only
“Toxicological studies were performed in mice using a surrogate murine anti-mouse C5 antibody (BB5.1 mAb).”
Why that species
Eculizumab binds only human C5; did not block hemolytic activity of any primate or non-primate serum tested
“Eculizumab did not effectively block haemolytic activity of sera from any primate or non-primate species tested, even at extremely high concentrations of antibody.”
Surrogate molecule
Yes: murine anti-mouse C5 antibody BB5.1, used for repeat-dose, fertility, embryo-fetal and pre/postnatal studies in mice
“Toxicological studies were performed in mice using a surrogate murine anti-mouse C5 antibody (BB5.1 mAb).”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“A twenty-six week study evaluated the toxicity of BB5.1 mAb.”
Pivotal GLP studies
26-week IV study of surrogate BB5.1 in CD-1 mice, once or twice weekly (30 or 60 mg/kg/week)
“Crl:CD-1®(ICR) BR mice received by IV route BB5.1 mAb at 0 mg/kg twice weekly, 30 mg/kg once weekly, or 30 mg/kg twice weekly (resulting in dose levels of 0, 30 and 60 mg/kg/week respectively).”
Route in tox
IV
“Crl:CD-1®(ICR) BR mice received by IV route BB5.1 mAb at 0 mg/kg twice weekly, 30 mg/kg once weekly, or 30 mg/kg twice weekly”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6)
“Non-clinical genotoxicity studies are not generally considered relevant to biotechnology products (ICH S6 guideline).”
Carcinogenicity
Not conducted; 26-week surrogate study showed no cytotoxic or proliferative activity suggestive of carcinogenic risk
“The 26-week repeat dose toxicity study with a murine anti-mouse C5 antibody (BB5.1mAb) showed no cytotoxic or proliferative activities suggestive of carcinogenic risk at dose levels up to 60 mg/kg/week”
Reproductive & developmental
Mouse surrogate fertility, EFD, PPND: no fertility effects; retinal dysplasia and umbilical hernia at high dose; more male offspring deaths
“When maternal exposure to the antibody occurred during organogenesis, two cases of retinal dysplasia and one case of umbilical hernia were observed among 230 offspring born to mothers exposed to the higher antibody dose; however, the exposure did not increase fetal loss or neonatal death.”
Safety pharmacology
No nonclinical safety pharmacology studies; justified by species specificity and clinical data
“No specific nonclinical safety pharmacology studies have been conducted.”
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 Soliris 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: Surrogate 26-week mouse study: no treatment effects on any toxicity parameter at either dose; no target organs (EMA assessment report, p. 9)
NOAEL / key findings
Surrogate 26-week mouse study: no treatment effects on any toxicity parameter at either dose; no target organs
“Treatment did not affect any of the toxicity parameters examined.”
Risksopen answer page →
Immune & cytokine safety
No lymph node findings with surrogate in 26-week mouse study; no dedicated immunotoxicity or cytokine studies
“There were no remarkable macroscopic observations or histomorphological findings in mandibular or mesenteric lymph nodes related to treatment with the surrogate antibody, BB5.1 mAb, in the twenty six week mouse study.”
Biodistribution & persistence
TCR: C5 staining of smooth/skeletal muscle, myoepithelium, myofibroblasts, renal tubular epithelium, reticulum cells; no distribution studies
“Eculizumab binds to C5 on smooth muscle (intrinsic/vascular) and skeletal muscle, myoepithelium, myofibroblasts, renal tubular epithelium, and reticulum cells.”
Modality-specific risk
Infections from terminal complement blockade, especially meningococcal; hemolysis after discontinuation
“Identified and potential risks are general infections, especially meningococcal infections, haemolysis after drug discontinuation and haematologic abnormalities.”
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