Enhanced Prenatal and Postnatal Development Study in Marmoset Monkeys Following Administration of Felzartamab.

Abstract

Felzartamab is a recombinant fully human immunoglobulin G1 anti-CD38 monoclonal antibody under clinical investigation for immune-mediated diseases. In support of felzartamab clinical development, toxicology studies were conducted in marmoset monkeys, which was the most relevant species based on CD38 binding affinity, pharmacologic activity, and target expression. The felzartamab toxicology program included an enhanced prenatal and postnatal development (ePPND) study to identify potential reproductive and postnatal development risks. In this ePPND study, pregnant marmoset monkeys were randomized to receive vehicle (0 mg/kg) or felzartamab at two dose levels (15 mg/kg and 75 mg/kg) twice per week until parturition, and maternal animals and infants were evaluated for 6 months thereafter. Felzartamab exposure was confirmed in maternal animals and infants in both dosing groups. Overall, felzartamab was well tolerated by pregnant animals at the evaluated doses, with no effect on body weight or body weight gain during pregnancy. No felzartamab-related effects on pregnancy loss or stillbirth rate were observed, and litter counts and numbers of liveborn infants were similar between the vehicle and felzartamab groups. Among infants, there were no felzartamab-related malformations or variations in external anatomy or skeletal morphology and no felzartamab-related observations in histopathology, hematologic and immune cell development, or humoral immune response to vaccination. In conclusion, among pregnant marmoset monkeys dosed with felzartamab, the lack of reproductive toxicity and felzartamab-related effects on offspring supports the clinical evaluation of felzartamab in women of childbearing potential and further demonstrates the suitability of the marmoset monkey for ePPND studies.