Adakveo (crizanlizumab): which tox species, and why?

Cynomolgus monkey only (Source: FDA multi-discipline review, p. 30.)

Precedia/Monoclonal antibodies/Adakveo/Species

Adakveo: which tox species, and why?

crizanlizumab · P-selectin

Check my plan vs. these

Species

Cynomolgus monkey only

“The toxicity of crizanlizumab was evaluated in GLP-compliant 4- and 26-week toxicology studies in cynomolgus monkeys.”

✓ VerifiedFDA multi-discipline review, p. 30Source ↗

Why that species

Binds human and cynomolgus platelet P-selectin; no binding to dog or rat P-selectin

“Crizanlizumab bound to human and cynomolgus monkey platelets expressing P-selectin, but did not bind to platelets expressing P-selectin from dog or rat. Thus, monkey is an appropriate toxicological animal model to study crizanlizumab.”

✓ VerifiedFDA multi-discipline review, p. 34Source ↗

Surrogate molecule

No surrogate; the clinical antibody (earlier SelG1 material and commercial SEG101) was tested in cynomolgus monkeys

“The preclinical safety profile of crizanlizumab was mostly characterised using the previous CHO-K1-derived material (SelG1) in Cynomolgus monkeys. The current crizanlizumab SEG101 was tested in the enhanced pre- and postnatal developmental toxicity study.”

✓ VerifiedEMA assessment report, p. 37Source ↗

Species: general tox

Cynomolgus monkey only (GLP 4- and 26-week studies)

“The toxicity of crizanlizumab was evaluated in GLP-compliant 4- and 26-week toxicology studies in cynomolgus monkeys.”

✓ VerifiedFDA multi-discipline review, p. 30Source ↗

Species: DART

Cynomolgus monkey enhanced PPND only; fertility assessed in 26-week monkey study, no separate fertility/early embryonic study

“The reproductive and developmental toxicology program includes one study, an enhanced pre- and postnatal developmental toxicity study. No separate studies for fertility or early embryonic development were conducted.”

✓ VerifiedEMA assessment report, p. 39Source ↗

Species: carcinogenicity

Not conducted (ICH S6); weight-of-evidence risk assessment instead

“In line with the ICH S6 (R1) guideline for the preclinical safety evaluation of biotechnology-derived pharmaceuticals, carcinogenicity studies with crizanlizumab have not been conducted.”

✓ VerifiedEMA assessment report, p. 38Source ↗

Surrogate used in

No surrogate used; earlier SelG1 material for general toxicity and current SEG101 for ePPND

✓ VerifiedEMA assessment report, p. 37Source ↗

Summary across all 117 monoclonal antibodies →

Adakveo: which tox species, and why?

Same question, other monoclonal antibodies