Design of a global, multicenter study to assess maternal, fetal, and infant outcomes of pegvaliase exposure during pregnancy and breastfeeding

Background: Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficiency of phenylalanine hydroxylase (PAH), which converts phenylalanine (Phe) to tyrosine. PAH deficiency leads to abnormally high levels of Phe that are toxic to the brain. Elevated Phe levels during pregnancy are associated with increased risk for pregnancy loss, major birth defects, and intellectual disability in children. Pegvaliase (Palynziq®) is a medicinal form of phenylalanine ammonia lyase administered subcutaneously to reduce Phe levels. Although pegvaliase clinical trials have demonstrated an acceptable benefit-risk profile, there are no well-controlled studies on the effects on pregnancy and offspring associated with pegvaliase exposure during pregnancy and breastfeeding.

Methods: PALomino (NCT05579548) is an observational, prospective, multicenter study of women with PKU exposed to pegvaliase during pregnancy. The objective of this study is to assess the frequency of pregnancy outcomes among women with PKU treated with pegvaliase during pregnancy and fetal/infant outcomes, intrauterine growth, preterm birth, failure to thrive, and developmental delays in their offspring. This study will enroll pregnant women diagnosed with PKU who have been treated with pegvaliase from 2 weeks prior to last menstrual period (LMP) or at any time during pregnancy.

Participants will be enrolled and followed for up to 21 months. Pegvaliase exposure will be collected for at least 3 months prior to LMP, during pregnancy and breastfeeding, and among participants with live-birth outcomes who initiate breastfeeding and breastfeed up to infant age 12 months. Fetal outcomes will be correlated to pegvaliase exposure and blood Phe levels.

Results: The study is currently open to enrollment in the US and is planned to open to enrollment in Europe in 2023.

Conclusions: These results will increase knowledge about the safety of pegvaliase during pregnancy and breastfeeding.