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The Cochrane Database of Systematic... Mar 2015Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
SEARCH METHODS
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Date of last search: 11 August 2014.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 4 September 2014We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
SELECTION CRITERIA
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data.
MAIN RESULTS
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 μmol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 μmol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS
There is evidence of short-term benefit from using sapropterin in some people with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
Topics: Adult; Biopterins; Child; Child, Preschool; Humans; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 25812600
DOI: 10.1002/14651858.CD008005.pub4 -
The Cochrane Database of Systematic... Jun 2010Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most... (Review)
Review
BACKGROUND
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria.
OBJECTIVES
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
SEARCH STRATEGY
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Last search:07 May 2010.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 01 September 2009.We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
SELECTION CRITERIA
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data.
MAIN RESULTS
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 mumol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 mumol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS
There is evidence of short-term benefit from using sapropterin in some patients with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
Topics: Adult; Biopterins; Child; Humans; Phenylalanine; Phenylketonurias
PubMed: 20556789
DOI: 10.1002/14651858.CD008005.pub2 -
Drugs 2009Sapropterin dihydrochloride (Kuvan), hereafter referred to as sapropterin, is a synthetic formulation of the active 6R-isomer of tetrahydrobiopterin, a naturally... (Review)
Review
UNLABELLED
Sapropterin dihydrochloride (Kuvan), hereafter referred to as sapropterin, is a synthetic formulation of the active 6R-isomer of tetrahydrobiopterin, a naturally occurring cofactor for phenylalanine hydroxylase. In the EU, sapropterin is approved for the treatment of hyperphenylalaninaemia in patients >or=4 years of age with tetrahydrobiopterin-responsive phenylketonuria (PKU) and in adults and children with tetrahydrobiopterin deficiency who have been shown to be responsive to such treatment. In the US, it is approved to reduce blood phenylalanine levels in patients with hyperphenylalaninaemia due to tetrahydrobiopterin-responsive PKU. Oral sapropterin effectively lowers blood phenylalanine levels in a proportion of patients with PKU; to date, there are no published efficacy trials of the specific sapropterin formulation under review in patients with tetrahydrobiopterin deficiency. Sapropterin was well tolerated in patients with PKU, although longer-term tolerability data are required. Sapropterin is the first non-dietary treatment for patients with PKU that has been shown in randomized, double-blind trials to be effective in lowering blood phenylalanine levels. Thus, sapropterin provides a promising treatment option for patients with PKU who are tetrahydrobiopterin-responsive. PHARMACOLOGICAL PROPERTIES: The mechanism of action of sapropterin in lowering blood phenylalanine levels in patients with PKU has not been fully elucidated, but appears to be related, in part, to its effect in augmenting and stabilizing mutant phenylalanine hydroxylases, resulting in increased clearance of phenylalanine from the body. In tetrahydrobiopterin deficiency, its mechanism of action is presumed to be secondary to replacement of endogenous tetrahydrobiopterin. In healthy adults, orally-administered sapropterin is absorbed into the bloodstream, reaching maximum concentrations in 3-4 hours. It has a mean elimination half-life of approximately 4 hours in healthy adults and, based on a population pharmacokinetic study, 6.7 hours in patients with tetrahydrobiopterin-responsive PKU. Age, from 9 to 49 years, had no effect on key pharmacokinetic parameters. THERAPEUTIC EFFICACY: In an 8-day screening study in patients aged >or=8 years with PKU, approximately 20% of patients responded to sapropterin 10 mg/kg/day (i.e. were tetrahydrobiopterin responsive). Tetrahydrobiopterin-responsive patients from this study were entered into a randomized, double-blind, placebo-controlled trial in which they received sapropterin 10 mg/kg/day or placebo. At the end of 6 weeks of treatment, sapropterin recipients experienced a significant 28% decrease from baseline in mean blood phenylalanine level, while there was no significant change in placebo recipients. The difference in mean blood phenylalanine level between sapropterin and placebo groups was statistically significant at -245 micromol/L. In an extension of this trial, significantly greater reductions in blood phenylalanine levels were observed with sapropterin dosages of 10 and 20 mg/kg/day than with sapropterin 5 mg/kg/day (each dose administered for 2 weeks), indicating a dose dependent effect. During 12 weeks of treatment with the sapropterin dosage individualized to the patient according to the earlier response to sapropterin 5, 10 or 20 mg/kg/day, reductions in plasma phenylalanine were observed in all dosage groups. In a randomized, double-blind trial in children aged 4-12 years with tetrahydrobiopterin-responsive PKU, patients treated with sapropterin 20 mg/kg/day had reduced blood phenylalanine levels after 3 weeks of treatment. Over the full 10-week trial, sapropterin and placebo recipients experienced a significantly increased tolerance to dietary phenylalanine (20.9 mg/kg/day in sapropterin and 2.9 mg/kg/day in placebo recipients).
TOLERABILITY
Sapropterin was well tolerated in patients with PKU. In clinical trials in patients with PKU, the following adverse events were identified: headache, rhinorrhoea (both at a frequency of >or=10%), pharyngolaryngeal pain, nasal congestion, cough, diarrhoea, vomiting, abdominal pain and hypophenylalaninaemia (all at a frequency of >or=1% to <10%). There were no serious adverse events that were thought to be related to sapropterin treatment.
Topics: Biopterins; Dose-Response Relationship, Drug; Half-Life; Humans; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 19323589
DOI: 10.2165/00003495-200969040-00006 -
Expert Opinion on Drug Metabolism &... Sep 2013Phenylketonuria (PKU) is caused by mutation of the enzyme, phenylalanine (Phe) hydroxylase (PAH). The hyperphenylalaninemia characteristic of PKU causes devastating... (Review)
Review
INTRODUCTION
Phenylketonuria (PKU) is caused by mutation of the enzyme, phenylalanine (Phe) hydroxylase (PAH). The hyperphenylalaninemia characteristic of PKU causes devastating neurological damage if not identified and treated at birth with a Phe-restricted diet. Sapropterin dihydrochloride, a pharmaceutical formulation of the natural cofactor for PAH (6R-tetrahydrobiopterin; BH4), is now available for the management of hyperphenylalaninemia in some PKU patients, including BH4 deficiencies. Sapropterin dihydrochloride improves dietary Phe tolerance in about 20% of patients with PKU.
AREAS COVERED
This evaluation describes the identification of patients suitable for treatment of sapropterin dihydrochloride, together with its indications, therapeutic properties and efficacy. Furthermore, the article reviews its safety and tolerability in patients with PKU or BH4 deficiency.
EXPERT OPINION
A reduction in blood Phe of at least 30% occurred in ∼ 20 - 30% of sapropterin-treated PKU patients (mostly with milder forms of PKU). Treatment with sapropterin resulted in clinically significant and sustained reductions in blood Phe concentrations and increased dietary Phe tolerance in well-designed clinical studies in PKU patients who responded to BH4. Successful treatment with sapropterin may lead to a relaxation of the Phe-restricted diet, although continued monitoring of blood Phe is required. Sapropterin was well tolerated.
Topics: Biopterins; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Humans; Mutation; Phenylalanine Hydroxylase; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 23705856
DOI: 10.1517/17425255.2013.804064 -
The Cochrane Database of Systematic... Dec 2012Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria.
OBJECTIVES
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
SEARCH METHODS
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Date of last search: 29 June 2012.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 23 July 2012.We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
SELECTION CRITERIA
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data.
MAIN RESULTS
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 μmol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 μmol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS
There is evidence of short-term benefit from using sapropterin in some patients with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
Topics: Adult; Biopterins; Child; Humans; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 23235653
DOI: 10.1002/14651858.CD008005.pub3 -
The Annals of Pharmacotherapy Sep 2009To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data,... (Review)
Review
OBJECTIVE
To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile of sapropterin for this indication.
DATA SOURCES
A literature search was conducted using MEDLINE (1966-May 2009), International Pharmaceutical Abstracts (1970-May 2009), and Cochrane database (2008) for the following key words: sapropterin, tetrahydrobiopterin, phenylketonurias, and phenylalanine.
STUDY SELECTION AND DATA EXTRACTION
English-language studies involving humans examining the role of tetrahydrobiopterin (BH4) in the management of PKU were reviewed to evaluate the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile for sapropterin. All Phase 2 and 3 randomized controlled trials assessing the safety and efficacy of sapropterin were included in this literature evaluation.
DATA SYNTHESIS
Sapropterin represents the only Food and Drug Administration-approved medication for BH4-responsive PKU, marking an important advance in the treatment of this condition. Among individuals with hyperphenylalaninemia and some residual phenylalanine hydroxylase function, sapropterin can enhance activity of this enzyme to decrease serum phenylalanine concentrations. Sapropterin has been compared with placebo in one Phase 2 and one Phase 3 clinical trial, demonstrating significantly better response rates. Based on available studies, this agent appears to be safe and well tolerated, with adverse event rates similar to those of placebo. However, additional studies are warranted to assess the long-term safety and efficacy of sapropterin therapy.
CONCLUSIONS
Sapropterin offers a promising therapeutic option for select individuals with BH4-responsive PKU, although long-term data are limited evaluating its safety and efficacy in traditional clinical practice settings. When considering sapropterin therapy, clinicians must consider factors such as cost and patient adherence to drug therapy and/or diet.
Topics: Biopterins; Humans; Phenylalanine; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 19654333
DOI: 10.1345/aph.1M050 -
Medecine Sciences : M/S 2020The prognosis for phenylketonuria (PKU) has been improved by neonatal screening and dietary management via a low-phenylalanine diet. This treatment must be followed... (Review)
Review
The prognosis for phenylketonuria (PKU) has been improved by neonatal screening and dietary management via a low-phenylalanine diet. This treatment must be followed throughout life, which induces severe compliance problems. Drug treatment with sapropterin (or BH4) has come to help a reduced percentage of patients who respond to this drug. A subcutaneous enzyme therapy is available in the USA and has obtained European marketing authorization, but generates significant side effects, which limits its effectiveness. New therapeutic options for PKU are currently being developed, in particular gene therapy. The purpose of this article is to take stock of the pathophysiology and the various new therapeutic modalities currently in development.
Topics: Biopterins; Diet; Genetic Therapy; Humans; Infant, Newborn; Neonatal Screening; Phenylketonurias; Prognosis; Therapies, Investigational
PubMed: 32821049
DOI: 10.1051/medsci/2020127 -
Neurotherapeutics : the Journal of the... Jul 2021Depletion of the enzyme cofactor, tetrahydrobiopterin (BH4), in T-cells was shown to prevent their proliferation upon receptor stimulation in models of allergic... (Observational Study)
Observational Study
Depletion of the enzyme cofactor, tetrahydrobiopterin (BH4), in T-cells was shown to prevent their proliferation upon receptor stimulation in models of allergic inflammation in mice, suggesting that BH4 drives autoimmunity. Hence, the clinically available BH4 drug (sapropterin) might increase the risk of autoimmune diseases. The present study assessed the implications for multiple sclerosis (MS) as an exemplary CNS autoimmune disease. Plasma levels of biopterin were persistently low in MS patients and tended to be lower with high Expanded Disability Status Scale (EDSS). Instead, the bypass product, neopterin, was increased. The deregulation suggested that BH4 replenishment might further drive the immune response or beneficially restore the BH4 balances. To answer this question, mice were treated with sapropterin in immunization-evoked autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Sapropterin-treated mice had higher EAE disease scores associated with higher numbers of T-cells infiltrating the spinal cord, but normal T-cell subpopulations in spleen and blood. Mechanistically, sapropterin treatment was associated with increased plasma levels of long-chain ceramides and low levels of the poly-unsaturated fatty acid, linolenic acid (FA18:3). These lipid changes are known to contribute to disruptions of the blood-brain barrier in EAE mice. Indeed, RNA data analyses revealed upregulations of genes involved in ceramide synthesis in brain endothelial cells of EAE mice (LASS6/CERS6, LASS3/CERS3, UGCG, ELOVL6, and ELOVL4). The results support the view that BH4 fortifies autoimmune CNS disease, mechanistically involving lipid deregulations that are known to contribute to the EAE pathology.
Topics: Adolescent; Adult; Aged; Animals; Biopterins; Brain; Cells, Cultured; Cross-Sectional Studies; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Multiple Sclerosis; Neopterin; Young Adult
PubMed: 33844153
DOI: 10.1007/s13311-021-01043-4 -
Molecular Genetics and Metabolism May 2019Phenylketonuria (PKU) is an inherited metabolic disease caused by phenylalanine hydroxylase (PAH) deficiency. As the resulting high blood phenylalanine (Phe)... (Review)
Review
Phenylketonuria (PKU) is an inherited metabolic disease caused by phenylalanine hydroxylase (PAH) deficiency. As the resulting high blood phenylalanine (Phe) concentration can have detrimental effects on brain development and function, international guidelines recommend lifelong control of blood Phe concentration with dietary and/or medical therapy. Sapropterin dihydrochloride is a synthetic preparation of tetrahydrobiopterin (6R-BH4), the naturally occurring cofactor of PAH. It acts as a pharmacological chaperone, reducing blood Phe concentration and increasing dietary Phe tolerance in BH4-responsive patients with PAH deficiency. Protocols to establish responsiveness to sapropterin dihydrochloride vary widely. Two meetings were held with an international panel of clinical experts in PKU management to develop recommendations for sapropterin dihydrochloride response testing. At the first meeting, regional differences and similarities in testing practices were discussed based on guidelines, a literature review, outcomes of a global physician survey, and case reports. Statements developed based on the discussions were sent to all participants for consensus (>70% of participants) evaluation using a 7-level rating system, and further discussed during the second meeting. The experts recommend sapropterin dihydrochloride response testing in patients with untreated blood Phe concentrations of 360-2000 μmol/L, except in those with two null mutations. For neonates, a 24-h sapropterin dihydrochloride loading test is recommended; responsiveness is defined as a decrease in blood Phe ≥30%. For older infants, children, adolescents, and adults, a test duration of ≥48 h or a 4-week trial is recommended. The main endpoint for a 48-h to 7-day trial is a decrease in blood Phe, while improved Phe tolerance is the endpoint to be assessed during a longer trial. Longer trials may not be feasible in some locations due to lack of reimbursement for hospitalization, while a 4-week trial may not be possible due to limited access to sapropterin dihydrochloride or public health regulation. A 48-h response test should be considered in pregnant patients who cannot achieve blood Phe ≤360 μmol/L with a Phe-restricted diet. Durability of response and clinical benefits of sapropterin dihydrochloride should be assessed over the long term. Harmonization of protocols is expected to improve identification of responders and comparability of test results worldwide.
Topics: Biopterins; Consensus; Diet; Female; Humans; Internationality; Phenylketonurias; Physicians; Practice Guidelines as Topic; Pregnancy
PubMed: 31103398
DOI: 10.1016/j.ymgme.2019.04.004 -
Pediatrics International : Official... Jan 2022The 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...
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.
Topics: Biopterins; Child, Preschool; Female; Humans; Japan; Male; Phenylalanine; Phenylketonurias; Pregnancy; Product Surveillance, Postmarketing
PubMed: 34331785
DOI: 10.1111/ped.14939