Ebanga
ansuvimab
Sources:FDA integrated review ↗
Species
Monkey
Longest study
4 wk
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
Rhesus monkey only
“The ansuvimab-zykl nonclinical safety studies included a good laboratory practice (GLP) 4 week, intravenous, repeat-dose toxicology study in rhesus monkeys”
Why that species
Rhesus monkey is the lethal EBOV challenge model used for proof of concept
“The activity of ansuvimab-zykl was evaluated in three in vivo proof-of-concept studies in which rhesus monkeys were challenged with uniformly lethal doses of Kikwit 8U EBOV (1000 pfu).”
Surrogate molecule
No surrogate; the clinical antibody was tested in rhesus monkeys
“No adverse ansuvimab-zykl-related findings were observed in the GLP 4-week toxicology study in rhesus monkeys up to the highest dose tested”
Study lengthopen answer page →
Longest pivotal study
4 weeks
“A 4-Week Intravenous Toxicity Study With an 8-Week Recovery Period in Rhesus Monkeys (Study #1016-1363):”
Pivotal GLP studies
GLP 4-week IV repeat-dose study in rhesus monkeys, with recovery groups
“A 4-Week Intravenous Toxicity Study With an 8-Week Recovery Period in Rhesus Monkeys (Study #1016-1363):”
Route in tox
IV (bolus and infusion)
“Drug was administered by IV bolus to low-dose and mid-dose animals, and by IV infusion to control and high-dose animals.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genotoxicity studies have not been conducted with ansuvimab-zykl. In accordance with International Council for Harmonisation (ICH) S6(R1), genotoxicity studies are not required for biologics.”
Carcinogenicity
Not conducted; not required for single-dose IV administration (ICH S1A, S6(R1))
“In accordance with ICH S1A and ICH S6(R1), carcinogenicity studies are not required as ansuvimab-zykl will be administered as a single intravenous (IV) infusion.”
Reproductive & developmental
Not conducted; generally not required for biologics to exogenous targets (ICH S6(R1))
“Dedicated reproductive toxicology studies have not been conducted with ansuvimab-zykl. In accordance with ICH S6(R1), reproductive toxicology studies are generally not required for biologics to exogenous targets.”
Safety pharmacology
ECG, blood pressure, respiratory rate and neurological exam within 4-week monkey study; no drug-related changes
“Assessments of safety pharmacology (electrocardiography, blood pressure, respiratory rate, and a neurological evaluation) were performed in the 4-week repeat-dose toxicology study in rhesus monkeys (Study #1016-1363).”
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 Ebanga 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 500 mg/kg/dose (highest dose); no adverse drug-related toxicity; 7.6-fold AUC margin (FDA integrated review, p. 85)
NOAEL / key findings
NOAEL 500 mg/kg/dose (highest dose); no adverse drug-related toxicity; 7.6-fold AUC margin
“NOAEL =500 mg/kg/dose (AUClast =222664 µg.day/mL at Day 22, gender-averaged) Exposure multiple =7.6”
Risksopen answer page →
Immune & cytokine safety
No exposure or activity changes suggesting meaningful anti-drug antibody formation in monkeys
“No clear changes in drug exposure or ex vivo EBOV GP binding activity were observed in this study, suggesting that no meaningful anti-drug antibody formation occurred in this study.”
Biodistribution & persistence
No off-target binding in normal human tissue cross-reactivity study
“No off-target binding was observed with ansuvimab-zykl in any tissue under the conditions of this study.”
Modality-specific risk
Potential immunogenicity, as with all therapeutic proteins
“As with all therapeutic proteins, there is potential for immunogenicity.”
Similar precedents
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