Enspryng
satralizumab
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 pivotal studies were conducted in cynomolgus monkey, the only pharmacologically relevant species.”
Why that species
Cross-reacts with cynomolgus IL-6R but not mouse or rat IL-6R
“Satralizumab showed cross-reactivity in cynomolgus monkey but not in mice or rats. Based on these data, monkey was selected as the relevant species for nonclinical testing of satralizumab.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys (mouse homolog judged not feasible due to immunogenicity)
“Carcinogenicity studies of satralizumab were not conducted because satralizumab does not bind to rat or mouse IL-6R, and the use of a mouse homolog antibody was determined not to be feasible because of immunogenicity.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“In general toxicity studies in monkey, weekly subcutaneous doses of up to 50 mg/kg for 4 or 26 weeks resulted in no notable toxicity or effects on male (sperm analysis) and female (menstrual cycle) reproductive parameters and organs.”
Pivotal GLP studies
Cynomolgus monkey 4- and 26-week studies, weekly SC up to 50 mg/kg; monkey ePPND
“In general toxicity studies in monkey, weekly subcutaneous doses of up to 50 mg/kg for 4 or 26 weeks resulted in no notable toxicity or effects on male (sperm analysis) and female (menstrual cycle) reproductive parameters and organs.”
Route in tox
Subcutaneous
“In the general toxicity studies, no adverse effects were observed in monkeys administered satralizumab (0, 2, 10, or 50 mg/kg/week SC) for 4 or 26 weeks.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (antibodies unable to interact with genetic material)
“No genotoxicity studies of satralizumab were conducted because antibodies are generally unable to interact with genetic material.”
Carcinogenicity
Not conducted (no rodent IL-6R binding; mouse homolog not feasible); human malignancy risk unknown
“Carcinogenicity studies of satralizumab were not conducted because satralizumab does not bind to rat or mouse IL-6R, and the use of a mouse homolog antibody was determined not to be feasible because of immunogenicity.”
Reproductive & developmental
Monkey ePPND (0, 2, 50 mg/kg/week SC): dose-dependent reduction in infant antibody responses to antigen challenge
“In the ePPND study, administration of satralizumab (0, 2, and 50 mg/kg/week SC) to pregnant females resulted in a dose-dependent reduction in the antibody responses to antigenic challenge in infants.”
Safety pharmacology
Incorporated into pivotal monkey toxicology studies
“No stand-alone safety pharmacology studies of satralizumab were submitted. Safety pharmacology assessments were incorporated into the pivotal toxicology studies of satralizumab in monkey.”
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 Enspryng 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 50 mg/kg/week (high dose) in 26-week SC monkey study; no notable toxicity (FDA pharmacology/toxicology review, p. 32)
NOAEL / key findings
NOAEL 50 mg/kg/week (high dose) in 26-week SC monkey study; no notable toxicity
“The NOAEL was the high dose of 50 mg/kg/week.”
Risksopen answer page →
Immune & cytokine safety
Low cytokine release syndrome risk in human whole-blood cytokine assay
“Based on a human in vitro blood cytokine assay, the potential of satralizumab to induce a cytokine release syndrome (CRS) is considered to be low in terms of incidence and increase in cytokines.”
Biodistribution & persistence
TCR: similar human and monkey staining consistent with IL-6R expression (adrenal, liver, macrophages, lymphocytes)
“The staining pattern produced was consistent with what is known regarding IL-6R expression in e.g. adrenal cells, liver, macrophages, and lymphocytes, and the staining pattern was similar in human and Cynomolgus monkey tissue.”
Modality-specific risk
Immunosuppression from IL-6R blockade: impaired antibody responses in exposed infants (infection, vaccine response risk)
“However, infants of women treated with satralizumab during pregnancy may be at increased risk of adverse effects such as infection or impaired response to vaccinations.”