Vectibix
panitumumab
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
“Repeated dose general toxicity studies were conducted using intravenous administration of panitumumab to male and female cynomolgus monkeys.”
Why that species
Cross-reactivity supported the cynomolgus monkey as the toxicology species
“Cross reactivity supported the choice of the cynomolgus monkey for safety testing.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkeys
“Repeated dose general toxicity studies were conducted using intravenous administration of panitumumab to male and female cynomolgus monkeys.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“These studies had a dosing duration from 4 weeks to 6 months, and all used once-a-week dosing.”
Pivotal GLP studies
Monkey IV studies of 4 weeks to 6 months, once-weekly dosing
“These studies had a dosing duration from 4 weeks to 6 months, and all used once-a-week dosing.”
Route in tox
Intravenous
“Repeated dose general toxicity studies were conducted using intravenous administration of panitumumab to male and female cynomolgus monkeys.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted
“Panitumumab has not been evaluated in genotoxicity studies.”
Carcinogenicity
Not conducted
“No carcinogenicity or mutagenicity studies of panitumumab have been conducted.”
Reproductive & developmental
Monkey EFD: embryolethality and abortions at 1.25-5x human dose, no teratogenicity
“There were no fetal malformations or other evidence of teratogenesis noted in the offspring; however, significant increases in embryolethality and abortions occurred at doses of approximately 1.25 to 5 times the recommended human dose (based on body weight).”
Safety pharmacology
Single-dose monkey telemetry study (CV, respiratory, CNS): no clinical signs, no CNS or respiratory effects, no ECG effects
“In this study, no clinical signs related to panitumumab were observed. Neuro-behavioural tests did not reveal any effect on the central nervous system.”
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 Vectibix 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 oncology monoclonal antibodies (ICH S9)
In cancer patients the start dose should be pharmacologically active yet reasonably safe. A common small-molecule approach is one-tenth of the dose severely toxic to 10% of rodents, or one-sixth of the highest non-severely toxic dose in non-rodents.
“A common approach for many small molecules is to set a start dose at 1/10 the Severely Toxic Dose in 10% of the animals (STD 10) in rodents. If the non-rodent is the most appropriate species, then 1/6 the Highest Non-Severely Toxic Dose (HNSTD) is considered an appropriate starting dose.”
This product's starting point
NOAEL / key findings: Skin toxicity and diarrhoea were the primary toxicities, severe enough to cause unscheduled deaths (EMA assessment report, p. 9)
NOAEL / key findings
Skin toxicity and diarrhoea were the primary toxicities, severe enough to cause unscheduled deaths
“Toxicity to skin and diarrhoea was the primary toxicity of panitumumab in monkeys. These effects were severe enough to cause a significant number of unscheduled deaths.”
Risksopen answer page →
Immune & cytokine safety
Anti-panitumumab antibodies (MAHA) in 9/10 low-dose, 2/10 mid-dose and 1/10 high-dose monkeys
“Nine of ten monkeys in the low dose group were MAHA positive (Monkey anti-human antibody defined as anti-panitumumab antibody); frequency for MAHA positive was 2/10 and 1/10 in the mid and high dose groups.”
Biodistribution & persistence
No panitumumab binding in human or monkey cardiac tissue in formal tissue cross-reactivity studies
“Further, no binding of panitumumab was noted in human or monkey cardiac tissue in a formal tissue cross-reactivity studies which utilised optimised immunohistochemical techniques to assess specific panitumumab binding.”
Modality-specific risk
Skin toxicity and diarrhoea from EGFR signalling inhibition; embryo-fetal loss
“It is considered directly related to the pharmacological action of drugs that inhibit EGFR signalling.”