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Phenylketonuria is a rare inherited disorder that disrupts the metabolism of phenylalanine (Phe) to tyrosine by phenylalanine hydroxylase (PAH). Sapropterin dihydrochloride (Kuvan®) is approved for use in Europe to reduce blood Phe levels and improve Phe tolerance in sapropterin-responsive individuals. KAMPER (NCT01016392) is an observational, multinational registry assessing long-term safety and efficacy of sapropterin. Five hundred and seventy-six participants with PAH deficiency were enrolled from nine European countries (69 sites; December 2009-May 2016). Participants were aged <4 years (n = 11), 4 to <12 years (n = 329), 12 to <18 years (n = 141), and ≥18 years (n = 95) at enrolment. Overall, 401 (69.6%) participants experienced a total of 1960 adverse events; 61 events in 42 participants were serious, and two were considered sapropterin-related by the investigator. Mean (standard deviation) actual dietary Phe intake increased from baseline across all age groups: 957 (799) mg/day to a maximum of 1959 (1121) mg/day over a total study period of 11 years. Most participants exhibited an increase in Phe tolerance while blood Phe levels remained in the target range for their age (120-360 μmol/L for <12 years; 120-600 μmol/L for ≥12 years). Most participants exhibited normal growth for height, weight, and body mass index. No additional safety concerns were identified. As an observational study, limitations include variability in routine care practices and inconsistent availability of data. Long-term sapropterin use demonstrates a favourable safety profile in real-world settings and increases Phe tolerance in participants with PAH deficiency while maintaining blood Phe levels in the target ranges., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Infants born to mothers with phenylketonuria (PKU) may develop congenital abnormalities because of elevated phenylalanine (Phe) levels in the mother during pregnancy. Maintenance of blood Phe levels between 120 and 360 μmol/L reduces risks of birth defects. Sapropterin dihydrochloride helps maintain blood Phe control, but there is limited evidence on its risk-benefit ratio when used during pregnancy. Data from the maternal sub-registries-KAMPER (NCT01016392) and PKUDOS (NCT00778206; PKU-MOMs sub-registry)-were collected to assess the long-term safety and efficacy of sapropterin in pregnant women in a real-life setting. Pregnancy and infant outcomes, and the safety of sapropterin were assessed. Final data from 79 pregnancies in 57 women with PKU are reported. Sapropterin dose was fairly constant before and during pregnancy, with blood Phe levels maintained in the recommended target range during the majority (82%) of pregnancies. Most pregnancies were carried to term, and the majority of liveborn infants were reported as 'normal' at birth. Few adverse and serious adverse events were considered related to sapropterin, with these occurring in participants with high blood Phe levels. This report represents the largest population of pregnant women with PKU exposed to sapropterin. Results demonstrate that exposure to sapropterin during pregnancy was well-tolerated and facilitated maintenance of blood Phe levels within the target range, resulting in normal delivery. This critical real-world data may facilitate physicians and patients to make informed treatment decisions about using sapropterin in pregnant women with PKU and in women of childbearing age with PKU who are responsive to sapropterin., (© 2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)