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

Precedia/Monoclonal antibodies/Anthim/Tox package

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

obiltoxaximab · B. anthracis PA

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

Single-dose clinical escalation supported by monkey AUC margin: 10 mg/kg AUC ~50,000 µg·hr/mL vs human AUC 10,000 at 114 mg

“The 10 mg/kg dose to monkeys with an approximate AUC of 50,000 µg·hr/ml provides an appropriate margin of safety based upon the human AUC of 10,000 following a 114 mg dose of Anthim.”

✓ VerifiedFDA pharmacology/toxicology review, p. 53Source ↗

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

Rat IV study with doses on Days 1, 4 and 7 (about 1 week, GLP definitive); recovery phase not stated

“In the definitive study, 8 rats/sex/group were administered vehicle (saline), 3, 10, or 30 mg/kg by IV injection on Days 1, 4, and 7.”

✓ VerifiedFDA pharmacology/toxicology review, p. 100Source ↗

Pivotal GLP studies

Definitive GLP rat study: 3, 10, 30 mg/kg IV on Days 1, 4, 7; plus monkey IV infusion safety pharmacology/toxicology study

“In the definitive study, 8 rats/sex/group were administered vehicle (saline), 3, 10, or 30 mg/kg by IV injection on Days 1, 4, and 7.”

✓ VerifiedFDA pharmacology/toxicology review, p. 100Source ↗

DART package

Species: DART

Rabbit (EFD, pilot and definitive); fertility not studied

“Two studies, a pilot study and a definitive study, were performed in rabbits.”

✓ VerifiedFDA pharmacology/toxicology review, p. 71Source ↗

Reproductive & developmental

Rabbit EFD: maternal and developmental NOEL 32 mg/kg (highest dose); fertility not studied

“The No-Observed-Effect Level (NOEL) of ETI-204 for maternal and developmental toxicity was determined to be 32 mg/kg/dose, the highest dose tested”

✓ VerifiedFDA pharmacology/toxicology review, p. 101Source ↗

PPND / ePPND: when

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.

Carcinogenicity

Species: carcinogenicity

Not conducted

“Carcinogenicity, genotoxicity, and fertility studies have not been conducted with obiltoxaximab.”

✓ VerifiedUS prescribing informationSource ↗

Carcinogenicity model

Not conducted

“Carcinogenicity, genotoxicity, and fertility studies have not been conducted with obiltoxaximab.”

✓ VerifiedUS prescribing informationSource ↗

Carcinogenicity timing

Not conducted: carcinogenicity studies not performed

“Carcinogenicity, genotoxicity, and fertility studies have not been conducted with obiltoxaximab.”

✓ VerifiedUS prescribing informationSource ↗

Summary across all 117 monoclonal antibodies →

Anthim: 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