Evaluation of the Developmental Toxicity of Vedolizumab, an α₄β₇ Receptor Antagonist, in Rabbit and Nonhuman Primate

Area of Science:

• Pharmacology
• Developmental Toxicology
• Immunology

Background:

• Vedolizumab is an established treatment for inflammatory bowel diseases like ulcerative colitis and Crohn disease.
• It functions by targeting the α4β7 integrin, inhibiting gut-specific lymphocyte homing.
• Assessing its developmental safety is crucial for potential use in pregnant patients.

Purpose of the Study:

• To evaluate the potential effects of vedolizumab on maternal and embryo-fetal development.
• To assess vedolizumab's impact on infant development and postpartum parameters in preclinical models.

Main Methods:

• Standard preclinical toxicity studies were conducted in pregnant rabbits and cynomolgus monkeys.
• Animals received intravenous vedolizumab at various dose levels during critical developmental periods.
• Maternal health, fetal development, and postpartum infant parameters were monitored.

Main Results:

• No adverse effects on maternal body weight, food consumption, or reproductive parameters were observed in rabbits.
• Vedolizumab did not impact fetal survival, intrauterine growth, or cause embryo-fetal developmental toxicity in rabbits.
• Cynomolgus monkeys showed no increased prenatal loss, stillbirth, or maternal toxicity; low levels were detected in breast milk post-partum.

Conclusions:

• Vedolizumab administration during pregnancy did not demonstrate maternal or developmental toxicity in preclinical studies.
• The drug appears to have a favorable safety profile concerning developmental and reproductive toxicology.
• Findings support the safety of vedolizumab in the context of pregnancy, pending further clinical evaluation.