Sapropterin for phenylketonuria: A Japanese post-marketing surveillance study

Abstract

Background: The aim of this study was to assess the long-term safety and efficacy of sapropterin in a real-world setting in Japanese patients with tetrahydrobiopterin (BH4)-responsive phenylketonuria. Methods: This post-marketing surveillance study enrolled all of the patients in Japan with confirmed BH4-responsive PKU who were administrated sapropterin between July 2008 and October 2017. Patients were observed at least every 3 months during follow up, with key data collected on treatment exposure/duration, effectiveness according to physician’s judgement, serum phenylalanine levels, and adverse events. Results: Of 87 enrolled patients, 85 patients (male, 42.4%; outpatients, 96.5%) were included in the safety and efficacy analysis sets. Treatment started at age <4 years in 43 (50.6%) patients and the most common starting daily dose was 5–10 mg/kg (n = 41, 48.2%) with the overall duration of treatment between 0.2 and 17.2 years. Serum phenylalanine levels, according to loading tests, reduced from a baseline level of 9.66 mg/dL (range 0.48–36.80 mg/dL) by >30% in 84 patients. Treatment was deemed effective in 79 of 85 patients (92.9%, 95% confidence interval: 85.3–97.4). One patient (1.2%) experienced an adverse drug reaction (alanine aminotransferase increased) 50 days after the start of administration, which resolved without complications with continued treatment. Conclusions: Sapropterin appears well tolerated and highly effective in Japanese patients treated in a real-world setting, including those who start treatment at age <4 years and pregnant women.