Synagis
palivizumab
Species
no relevantMonkeyRat
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 repeat-dose studies; single-dose studies in rat and cynomolgus monkey only
“These results could be confirmed in Cynomolgus monkeys after a single administration of palivizumab.”
Why that species
Exogenous viral target; repeat-dose studies omitted owing to immunogenicity in animals and lack of human tissue binding
“The lack of repeated dose toxicity studies (including reproductive toxicity) was justified by the company by the immunogenicity of the human compound in animals and the lack of binding of the compound to a range of tissues.”
Surrogate molecule
No surrogate; the clinical antibody was tested in single-dose rat and cynomolgus monkey studies
“A single dose toxicity study of palivizumab administered to Sprague Dawley rats via intravenous injection including assessment of clinical signs, body weight changes, food consumption, ophthalmoscopy, haematology, clinical and anatomic pathology until 14 days post injection”
Study lengthopen answer page →
Longest pivotal study
0 (no repeat-dose studies; single-dose only)
“Studies on repeated dose toxicity, effects on the reproduction, embryo-foetal & perinatal toxicity, mutagenic potential, oncogenic/carcinogenic potential and ecotoxicity/environmental risk assessment were not considered necessary by the applicant and were not performed.”
Pivotal GLP studies
No repeat-dose studies; single IV dose in Sprague Dawley rats (14-day observation) and cynomolgus monkeys; no toxicity
“A single dose toxicity study of palivizumab administered to Sprague Dawley rats via intravenous injection including assessment of clinical signs, body weight changes, food consumption, ophthalmoscopy, haematology, clinical and anatomic pathology until 14 days post injection gave no indication of toxicity”
Route in tox
Intravenous (single-dose studies); local tolerance in rabbits
“A single dose toxicity study of palivizumab administered to Sprague Dawley rats via intravenous injection”
Skipped studiesopen answer page →
Genotoxicity
Not conducted
“Carcinogenesis, mutagenesis, and reproductive toxicity studies have not been performed.”
Carcinogenicity
Not conducted
“Carcinogenesis, mutagenesis, and reproductive toxicity studies have not been performed.”
Reproductive & developmental
Not conducted; product not indicated for adults or females of reproductive potential
“Pregnancy Category C: Synagis® 110 is not indicated for adult usage and animal reproduction studies have not been conducted.”
Safety pharmacology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
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 Synagis 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: No toxicity after single IV doses in rats and monkeys; no injection-site effects in rabbit local tolerance study (EMA assessment report, p. 5)
NOAEL / key findings
No toxicity after single IV doses in rats and monkeys; no injection-site effects in rabbit local tolerance study
“gave no indication of toxicity or statistically significant deviations from normal caused by the test article for the described parameters.”
Risksopen answer page →
Immune & cytokine safety
Immunogenic in cynomolgus monkeys: anti-drug antibodies in low- and high-dose groups
“Palivizumab was immunogenic in Cynomolgus monkeys and led to the generation of anti”
Biodistribution & persistence
No binding in tissue cross-reactivity study with pediatric human tissues
“No binding was observed in any of the tested human tissues.”
Modality-specific risk
Low target-related risk (viral antigen, no human tissue binding); hypersensitivity and anaphylaxis
“No binding was observed in any of the tested human tissues.”
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