TY - JOUR
T1 - Long-term safety and efficacy of sapropterin
T2 - The PKUDOS registry experience
AU - Longo, Nicola
AU - Arnold, Georgianne L.
AU - Pridjian, Gabriella
AU - Enns, Gregory M.
AU - Ficicioglu, Can
AU - Parker, Susan
AU - Cohen-Pfeffer, Jessica L.
N1 - Funding Information:
BioMarin Pharmaceutical Inc. manufactures and markets Kuvan ® (sapropterin dihydrochloride) which is the subject of this research. SP and JLCP are employees and shareholders of BioMarin Pharmaceutical Inc. NL, GA, GE are paid consultants and/or have received research grants from BioMarin Pharmaceutical Inc. GP and CF have no stated conflicts.
Publisher Copyright:
© 2015.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe) - from 591. ±. 382. μmol/L at baseline to 392. ±. 239. μmol/L (p = 0.0009) after 5. years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000. ±. 959. mg/day (pre-sapropterin baseline) to 1539. ±. 840. mg/day after 6. years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in ≤. 1% of subjects. Similar safety and efficacy data were observed for children. <. 4. years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance.
AB - The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe) - from 591. ±. 382. μmol/L at baseline to 392. ±. 239. μmol/L (p = 0.0009) after 5. years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000. ±. 959. mg/day (pre-sapropterin baseline) to 1539. ±. 840. mg/day after 6. years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in ≤. 1% of subjects. Similar safety and efficacy data were observed for children. <. 4. years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance.
KW - Phenylalanine
KW - Phenylketonuria
KW - Sapropterin
UR - http://www.scopus.com/inward/record.url?scp=84926421005&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2015.02.003
DO - 10.1016/j.ymgme.2015.02.003
M3 - Article
C2 - 25724073
AN - SCOPUS:84926421005
SN - 1096-7192
VL - 114
SP - 557
EP - 563
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 4
ER -