Evaluation of the effect of rozanolixizumab on pregnancy outcomes and pre- and postnatal development in cynomolgus monkeys.

Rozanolixizumab, a humanised immunoglobulin (Ig) G4 monoclonal antibody that selectively inhibits binding of IgG to the neonatal Fc receptor (FcRn), was evaluated in an embryo-foetal enhanced pre- and postnatal development (ePPND) study. Pregnant female cynomolgus monkeys (19 per group) received subcutaneous rozanolixizumab 50 mg/kg or 150 mg/kg or vehicle every 3 days from gestation day 20 until delivery. The proportion of pregnancy losses was 15.8%, 21.1% and 5.3% in the rozanolixizumab 50 mg/kg, 150 mg/kg and control groups, respectively. Based on eNormograms for groups of 18 or 20 animals, these results were considered to be within the range of spontaneous prenatal losses naturally observed in cynomolgus monkeys. Foetal examinations revealed no treatment-related effects. All infants had normal postnatal development, although higher mortality was observed in female infants from the control group during the first 3 weeks. All infants were able to mount a normal immune response to keyhole limpet haemocyanin when vaccinated at the age of 4 months. Offspring from 150 mg/kg-treated mothers had very low IgG levels at birth, indicating blockade of maternal IgG transfer; infants from mothers who received 50 mg/kg had variable IgG levels at birth, with mothers who had developed significant anti-drug antibodies conferring maternal IgG transfer to varying degrees. Rates of infection in infants were similar across treatment groups. IgG levels in infants from rozanolixizumab-treated groups normalised within 2 months. Treatment of pregnant cynomolgus monkeys with the FcRn inhibitor rozanolixizumab had no adverse effects on pre- or postnatal development of offspring, including immune system development.