Veopoz (pozelimab): what was done before first-in-human, and what came after?

Precedia/Monoclonal antibodies/Veopoz/Tox package

Veopoz: what was done before first-in-human, and what came after?

pozelimab · Complement C5

Before first-in-human

First-in-human: where

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.

Repeat-dose tox before first-in-human

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-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

Use pharmacology data (target binding, receptor occupancy, in vitro human cells, PK/PD modelling) to estimate the lowest dose expected to have any biological effect (MABEL) and the active dose (PAD), and, for healthy volunteers, start at an exposure below the PAD unless robustly justified.

“these data should be used to determine the minimal anticipated biological effect level (MABEL) in humans and an estimation of the pharmacologically active dose (PAD) and/or anticipated therapeutic dose range (ATD) in humans.”

✓ VerifiedEMA 2017: Guideline on strategies to identify and mitigate risks for…, p. 11Source ↗

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)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

26-week cynomolgus monkey (IV infusion) with 13-week recovery

“A 26-Week Intravenous Infusion Toxicity, Toxicokinetic, and Fertility Assessment Study in Sexually Mature Cynomolgus Monkeys with a 13-Week Recovery Phase”

✓ VerifiedFDA multi-discipline review, p. 40Source ↗

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”

✓ VerifiedFDA multi-discipline review, p. 39Source ↗

DART package

Species: DART

Cynomolgus monkey (enhanced pre- and postnatal development with juvenile dosing of offspring)

“Pozelimab is not pharmacologically active in rat or mouse. Thus, an enhanced pre- and postnatal development study was conducted with pozelimab in pregnant cynomolgus monkeys, with juvenile dosing of the offspring for three months post-weaning.”

✓ VerifiedFDA multi-discipline review, p. 41Source ↗

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”

✓ VerifiedFDA multi-discipline review, p. 36Source ↗

PPND / ePPND: when

ePPND in cynomolgus monkey with juvenile dosing of offspring completed before the marketing application

“Thus, an enhanced pre- and postnatal development study was conducted with pozelimab in pregnant cynomolgus monkeys, with juvenile dosing of the offspring for three months post-weaning.”

✓ VerifiedFDA multi-discipline review, p. 41Source ↗

Carcinogenicity

Species: carcinogenicity

Not conducted; ECAC agreed studies not necessary

“The Executive Carcinogenicity Assessment Committee concurred with the Applicant’s proposal that nonclinical carcinogenicity studies with pozelimab are not necessary to support a BLA for this product.”

✓ VerifiedFDA multi-discipline review, p. 41Source ↗

Carcinogenicity model

Not conducted; carcinogenicity risk assessment concluded low potential

“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.”

✓ VerifiedFDA multi-discipline review, p. 41Source ↗

Carcinogenicity timing

Not required: ECAC concurred studies not necessary for the BLA (weight-of-evidence)

“Carcinogenicity Assessment Committee concurred with the Applicant’s proposal that nonclinical carcinogenicity studies with pozelimab are not necessary to support a BLA for this product.”

✓ VerifiedFDA multi-discipline review, p. 41Source ↗

Summary across all 117 monoclonal antibodies →

Veopoz: what was done before first-in-human, and what came after?

Before first-in-human

Longest repeat-dose systemic studies

DART package

Carcinogenicity

Same question, other monoclonal antibodies