Long-term safety and efficacy of sapropterin: the PKUDOS registry experience.
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.
University of Utah, Division of Medical Genetics, Salt Lake City, UT 84108, USA.
Nicola
N
Longo
University of Pittsburgh School of Medicine, Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15238, USA.
Georgianne L
GL
Arnold
Tulane University School of Medicine, Hayward Genetics Center, New Orleans, LA 70112, USA.
Gabriella
G
Pridjian
Stanford University, Division of Medical Genetics, Stanford, CA 94305-5208, USA.
Gregory M
GM
Enns
The Children's Hospital of Philadelphia, Perelman School of Medicine,University of Pennsylvania, Philadelphia, PA 19104, USA.
Can
C
Ficicioglu
BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.
Susan
S
Parker
BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA. Electronic address: JCohen@bmrn.com.
Jessica L
JL
Cohen-Pfeffer
D000293:Adolescent; D000328:Adult; D001708:Biopterins / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004032:Diet; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood; D010661:Phenylketonurias / Q000188:drug therapy*; D012042:Registries; D013997:Time Factors; D014443:Tyrosine / Q000097:blood; D055815:Young Adult
D001708:Biopterins; D014443:Tyrosine; D010649:Phenylalanine; C003402:sapropterin
Phenylalanine; Phenylketonuria; Sapropterin