Raxibacumab
raxibacumab
Species
MonkeyRabbit
Longest study
3 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Partial / alternative Partial / alternative
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Healthy rabbit and cynomolgus monkey
“Drug safety assessed in human volunteers and in a battery of nonclinical studies in healthy rabbits and non-human primates showed no evidence of toxicity at the maximum proposed, single therapeutic dose of intravenous raxibacumab to be administered to human adults of 40 mg/kg.”
Why that species
Target is a bacterial toxin; rabbit and cynomolgus macaque are the inhalation anthrax efficacy models
“several drug efficacy studies of raxibacumab with and without antibiotic in inhalation anthrax animal models (NZW rabbit and cynomolgus macaque)”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys and rabbits
“Healthy cynomolgus macaques administered 3 intravenous doses or 3 subcutaneous doses of 40 mg/kg raxibacumab once every 12 days”
Study lengthopen answer page →
Longest pivotal study
3 weeks
“Healthy cynomolgus macaques administered 3 intravenous doses or 3 subcutaneous doses of 40 mg/kg raxibacumab once every 12 days”
Pivotal GLP studies
Healthy cynomolgus monkey: 3 IV or SC doses of 40 mg/kg every 12 days, or single IM dose; 120-day follow-up
“Healthy cynomolgus macaques administered 3 intravenous doses or 3 subcutaneous doses of 40 mg/kg raxibacumab once every 12 days, or a single intramuscular dose (40 mg/kg) of raxibacumab, showed no adverse effects, including no effects up to 120 days post-dosing.”
Route in tox
IV, SC and IM (monkey); IV (rabbit)
“Healthy cynomolgus macaques administered 3 intravenous doses or 3 subcutaneous doses of 40 mg/kg raxibacumab once every 12 days, or a single intramuscular dose (40 mg/kg) of raxibacumab”
Skipped studiesopen answer page →
Genotoxicity
Not conducted
“Carcinogenicity, genotoxicity, and fertility studies have not been conducted with raxibacumab.”
Carcinogenicity
Not conducted
“Carcinogenicity, genotoxicity, and fertility studies have not been conducted with raxibacumab.”
Reproductive & developmental
No fertility studies; rabbit EFD (IV up to 120 mg/kg, GD 7 and 14): no harm to dams or fetuses
“A single embryonic-fetal development study was conducted in pregnant, healthy New Zealand White rabbits administered two intravenous doses of raxibacumab up to 120 mg/kg (three times the human dose on a mg/kg basis) on gestation days 7 and 14. No evidence of harm to the pregnant dam or the fetuses due to raxibacumab was observed.”
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 Raxibacumab 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: Greater CNS lesion severity (bacteria, inflammation, hemorrhage) in anthrax-infected non-survivors given 40 mg/kg (FDA pharmacology/toxicology review, p. 7)
NOAEL / key findings
Greater CNS lesion severity (bacteria, inflammation, hemorrhage) in anthrax-infected non-survivors given 40 mg/kg
“Anthrax infected rabbits and monkeys administered an intravenous injection of raxibacumab (40 mg/kg) at time of PA toxemia reproducibly showed greater severity of CNS lesions (bacteria, inflammation, hemorrhage, and necrosis) in non-surviving animals compared to dead placebo control animals”
Risksopen answer page →
Immune & cytokine safety
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.
Biodistribution & persistence
No brain tissue cross-reactivity (rabbit, monkey, human); enters CNS only after blood-brain barrier compromise
“Studies with raxibacumab in rabbit, cynomolgus macaque, and human donor tissues showed no cross reactivity with brain.”
Modality-specific risk
Exaggerated CNS inflammation and hemorrhage in infected non-survivors after blood-brain barrier compromise
“The raxibacumab monoclonal antibody appears unable to penetrate the CNS until compromise of the blood brain barrier (BBB) during the later stages of anthrax infection.”
Similar precedents
Anthimobiltoxaximab · B. anthracis PAMonkey + rodent · 1 wkBeyfortusnirsevimab · RSV F proteinMonkey only · 4 wkEbangaansuvimab · Zaire ebolavirus glycoproteinMonkey only · 4 wkTrogarzoibalizumab · CD4Monkey only · 39 wkEnflonsiaclesrovimab · RSV F protein (site IV)Rodent only · 2 wkSynagispalivizumab · RSV F proteinNo relevant species · none