Veopoz
pozelimab
Sources:FDA multi-discipline review ↗
Species
Monkey
Longest study
26 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
Cynomolgus monkey only; not evaluated in rodents
“Thirteen- and 26-week repeat-dose toxicity studies were conducted with pozelimab in cynomolgus monkeys. As pozelimab is not pharmacologically active in rat or mouse, it was not evaluated in a rodent species.”
Why that species
Binds human and monkey C5 with high affinity but not mouse, rat or rabbit C5
“Pozelimab (REGN3918) is a human monoclonal antibody that binds with high affinity to complement factor 5 (C5) from human and monkey but not mouse, rat, or rabbit.”
Surrogate molecule
No surrogate in toxicology; C5 humanized transgenic mice used only for pharmacology; clinical antibody tested in monkeys
“serum samples from pozelimab-treated C5 humanized mice (i.e., transgenic mice expressing human C5) and monkeys resulted in > 80% inhibition of classical pathway-induced hemolysis.”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“Thirteen- and 26-week repeat-dose toxicity studies were conducted with pozelimab in cynomolgus monkeys.”
Pivotal GLP studies
GLP 13-week monkey study: IV 5, 20, 100 mg/kg or SC 100 mg/kg once weekly; plus 26-week IV study
“Dose and frequency of dosing: IV: 5, 20, 100 mg/kg; SC: 100 mg/kg; once weekly”
Route in tox
IV and SC
“No adverse effects of pozelimab were observed in repeat-dose toxicity studies at doses up to 100 mg/kg/week SC (13 weeks) or IV (26 weeks).”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6(R1))
“Genetic toxicology studies with pozelimab have not been conducted, in accordance with ICH S6(R1).”
Carcinogenicity
Not conducted; weight-of-evidence assessment concluded low carcinogenic potential; ECAC concurred
“Carcinogenicity studies with pozelimab have not been conducted. The Applicant conducted a carcinogenicity risk assessment for pozelimab and concluded that the carcinogenic potential is low.”
Reproductive & developmental
No fertility effects in 26-week study; monkey ePPND with juvenile dosing: no maternal, infant or juvenile effects up to 50 mg/kg/week
“No adverse effects of pozelimab were observed on male or female fertility parameters in the 26- week repeat-dose toxicity study at doses up to 100 mg/kg/week. Additionally, no adverse effects of pozelimab were observed on maternal or infant health or on juvenile development at doses up to 50 mg/kg/week”
Safety pharmacology
Incorporated into 13- and 26-week monkey studies; no effects on ECG, neurological or respiratory function
“Nonclinical studies conducted with pozelimab include pharmacology studies, pharmacokinetics, 13- and 26-week repeat-dose toxicity studies in cynomolgus monkeys with incorporated safety pharmacology endpoints”
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 Veopoz 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 100 mg/kg/week (highest dose) in 13- and 26-week monkey studies; no adverse findings; clinical margins 12-15 (FDA multi-discipline review, p. 36)
NOAEL / key findings
NOAEL 100 mg/kg/week (highest dose) in 13- and 26-week monkey studies; no adverse findings; clinical margins 12-15
“No adverse effects of pozelimab were observed in repeat-dose toxicity studies at doses up to 100 mg/kg/week SC (13 weeks) or IV (26 weeks). Clinical safety margins are 12-15 relative to the predicted drug exposure”
Risksopen answer page →
Immune & cytokine safety
ADA in 9 of 36 treated monkeys (26-week study); ADA did not notably affect exposure
“Nine of 36 treated animals were positive for ADA post-dose (7/12 LD animals, 2/12 HD animals). Positive ADA response did not notably affect drug exposure.”
Biodistribution & persistence
TCR: no plasma membrane staining; cytoplasmic staining unlikely relevant; off-target toxicity risk minimal
“No plasma membrane staining with pozelimab was observed. Given the low likelihood that pozelimab will enter the cytoplasm of cells and in the absence of adverse effects in the 13- and 26-week toxicity studies, the risk of off-target binding by pozelimab resulting in clinically relevant toxicity is minimal.”
Modality-specific risk
Serious infections, including meningococcal infections, from complement inhibition
“The increased risk of serious infections, including meningococcal infections associated with administration of pozelimab, will be included in the labeling as a Warning and Precaution.”
Similar precedents
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