Saphnelo
anifrolumab
Species
Monkey
Longest study
39 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
“All in vivo toxicity studies were conducted in cynomolgus monkeys which can be considered as a relevant species for evaluation of safety of anifrolumab.”
Why that species
Binding and neutralisation activity of anifrolumab in monkey cells
“Cynomolgus monkey was selected as the pharmacologically relevant toxicology model for nonclinical safety assessment based on binding and neutralisation activity of anifrolumab in monkey cells.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys
“All in vivo toxicity studies were conducted in cynomolgus monkeys which can be considered as a relevant species for evaluation of safety of anifrolumab.”
Study lengthopen answer page →
Longest pivotal study
39 weeks
“Repeat-dose toxicity of anifrolumab was evaluated in cynomolgus monkeys in 4-weeks and 39-weeks GLP toxicity studies with an additional recovery period of 7 or 12 weeks, respectively.”
Pivotal GLP studies
Cynomolgus monkey 4-week IV and 39-week IV/SC weekly GLP studies
“Repeat-dose toxicity of anifrolumab was evaluated in cynomolgus monkeys in 4-weeks and 39-weeks GLP toxicity studies with an additional recovery period of 7 or 12 weeks, respectively.”
Route in tox
IV (30-minute infusion) and SC, once weekly
“In this study, cynomolgus monkeys were given 40 IV infusion (30 minutes) doses of anifrolumab at 5 and 50 mg/kg/week once a week (QW) or 40 subcutaneous (SC) injection doses of anifrolumab at 15 and 60 mg/kg/week QW.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genetic toxicity studies have not been conducted with anifrolumab. Genetic toxicity studies are generally not applicable for biotechnology-derived pharmaceuticals such as anifrolumab, as discussed in the ICH S6(R1) guidance document.”
Carcinogenicity
Not conducted: anifrolumab does not bind murine IFNAR1 or inhibit murine IFN-α
“Carcinogenicity studies with anifrolumab were not conducted. Anifrolumab does not bind to murine IFNAR1 and does not inhibit the biological activity of murine IFN-α.”
Reproductive & developmental
Monkey ePPND: no maternal toxicity, embryo-fetal toxicity or postnatal developmental effects
“There was no evidence of anifrolumab-fnia related maternal toxicity, embryo-fetal toxicity, or post-natal developmental effects.”
Safety pharmacology
No stand-alone studies; ECG and blood pressure in 4- and 39-week monkey studies, no adverse CV findings; CNS/respiratory via clinical signs
“No stand-alone safety pharmacology studies were conducted with anifrolumab. The effect of anifrolumab on the CV system was evaluated in a GLP-compliant 39-week general IV toxicity study in monkeys (Study# 7140-129).”
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 Saphnelo 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: 39-week males: NOAEL below 5 mg/kg IV and 15 mg/kg SC due to arteritis; at least 50 IV/60 SC if arteritis excluded (EMA assessment report, p. 33)
NOAEL / key findings
39-week males: NOAEL below 5 mg/kg IV and 15 mg/kg SC due to arteritis; at least 50 IV/60 SC if arteritis excluded
“Based on the arterial inflammation observed, the NOAEL for males is less than 5 mg/kg IV and 15 mg/kg SC. If the observed arteritis is not factored into the NOAEL determination, the NOAEL of anifrolumab for males is at least 50 mg/kg IV and 60 mg/kg SC, the highest doses tested.”
Risksopen answer page →
Immune & cytokine safety
Arteritis in high-dose males attributed to ADA-mediated immune complex deposition (anifrolumab, IgM, C3b)
“The arteritis could be due to the deposit of ADA-mediated immunocomplexes based on positive staining of anifrolumab, monkey IgM, and complement component 3b (C3b) but not monkey IgG from kidney samples of 2 HD-IV monkeys with arteritis.”
Biodistribution & persistence
Infant monkey serum on day 30 after birth 4.2-9.7% of maternal concentrations
“In the infants, mean serum concentrations of anifrolumab‑fnia on Day 30 after birth increased with dose and were approximately 4.2% to 9.7% of the respective maternal concentrations.”
Modality-specific risk
Type I IFN blockade: plausible increased cancer risk given IFN anti-tumour role
“Type I interferons have a role in the anti-tumour response. Thus, it is plausible that blockade of IFNAR1 responses would potentially increase the risk of”