Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2months to 2years

Susan A. Berry, Nicola Longo, George A. Diaz, Shawn E. McCandless, Wendy E. Smith, Cary Harding, Roberto Zori, Can Ficicioglu, Uta Lichter-Konecki, Beth Robinson, Jerry Vockley

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2. months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. Methods: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2. months to 2. years were switched to, or started, GPB. Retrospective data up to 12. months pre-switch and prospective data during initiation of therapy were used as baseline measures. The primary efficacy endpoint of the integrated analysis was the successful transition to GPB with controlled ammonia (<. 100. μmol/L and no clinical symptoms). Secondary endpoints included glutamine and levels of other amino acids. Safety endpoints included adverse events, hyperammonemic crises (HACs), and growth and development. Results: 82% and 53% of patients completed 3 and 6. months of therapy, respectively (mean 8.85. months, range 6. days-18.4. months). Patients transitioned to GPB maintained excellent control of ammonia and glutamine levels. There were 36 HACs in 11 patients before GPB and 11 in 7 patients while on GPB, with a reduction from 2.98 to 0.88 episodes per year. Adverse events occurring in at least 10% of patients while on GPB were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash/papule. Conclusion: GPB was safe and effective in UCD patients aged 2. months to 2. years. GPB use was associated with good short- and long-term control of ammonia and glutamine levels, and the annualized frequency of hyperammonemic crises was lower during the study than before the study. There was no evidence for any previously unknown toxicity of GPB.

Original languageEnglish (US)
JournalMolecular Genetics and Metabolism
DOIs
StateAccepted/In press - 2017

Fingerprint

Inborn Urea Cycle Disorder
Urea
Safety
Glutamine
Ammonia
Nitrogen
glycerol phenylbutyrate
Amino Acids
Exanthema
Neutropenia
Growth and Development
Nose
Cough
Vomiting
Toxicity
Diarrhea
Fever

Keywords

  • Ammonia
  • Children
  • Glutamine
  • Glycerol phenylbutyrate
  • Infants
  • Urea cycle disorders

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2months to 2years. / Berry, Susan A.; Longo, Nicola; Diaz, George A.; McCandless, Shawn E.; Smith, Wendy E.; Harding, Cary; Zori, Roberto; Ficicioglu, Can; Lichter-Konecki, Uta; Robinson, Beth; Vockley, Jerry.

In: Molecular Genetics and Metabolism, 2017.

Research output: Contribution to journalArticle

Berry, SA, Longo, N, Diaz, GA, McCandless, SE, Smith, WE, Harding, C, Zori, R, Ficicioglu, C, Lichter-Konecki, U, Robinson, B & Vockley, J 2017, 'Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2months to 2years', Molecular Genetics and Metabolism. https://doi.org/10.1016/j.ymgme.2017.09.002
Berry, Susan A. ; Longo, Nicola ; Diaz, George A. ; McCandless, Shawn E. ; Smith, Wendy E. ; Harding, Cary ; Zori, Roberto ; Ficicioglu, Can ; Lichter-Konecki, Uta ; Robinson, Beth ; Vockley, Jerry. / Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2months to 2years. In: Molecular Genetics and Metabolism. 2017.
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abstract = "Introduction: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2. months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. Methods: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2. months to 2. years were switched to, or started, GPB. Retrospective data up to 12. months pre-switch and prospective data during initiation of therapy were used as baseline measures. The primary efficacy endpoint of the integrated analysis was the successful transition to GPB with controlled ammonia (<. 100. μmol/L and no clinical symptoms). Secondary endpoints included glutamine and levels of other amino acids. Safety endpoints included adverse events, hyperammonemic crises (HACs), and growth and development. Results: 82{\%} and 53{\%} of patients completed 3 and 6. months of therapy, respectively (mean 8.85. months, range 6. days-18.4. months). Patients transitioned to GPB maintained excellent control of ammonia and glutamine levels. There were 36 HACs in 11 patients before GPB and 11 in 7 patients while on GPB, with a reduction from 2.98 to 0.88 episodes per year. Adverse events occurring in at least 10{\%} of patients while on GPB were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash/papule. Conclusion: GPB was safe and effective in UCD patients aged 2. months to 2. years. GPB use was associated with good short- and long-term control of ammonia and glutamine levels, and the annualized frequency of hyperammonemic crises was lower during the study than before the study. There was no evidence for any previously unknown toxicity of GPB.",
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AU - Berry, Susan A.

AU - Longo, Nicola

AU - Diaz, George A.

AU - McCandless, Shawn E.

AU - Smith, Wendy E.

AU - Harding, Cary

AU - Zori, Roberto

AU - Ficicioglu, Can

AU - Lichter-Konecki, Uta

AU - Robinson, Beth

AU - Vockley, Jerry

PY - 2017

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N2 - Introduction: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2. months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. Methods: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2. months to 2. years were switched to, or started, GPB. Retrospective data up to 12. months pre-switch and prospective data during initiation of therapy were used as baseline measures. The primary efficacy endpoint of the integrated analysis was the successful transition to GPB with controlled ammonia (<. 100. μmol/L and no clinical symptoms). Secondary endpoints included glutamine and levels of other amino acids. Safety endpoints included adverse events, hyperammonemic crises (HACs), and growth and development. Results: 82% and 53% of patients completed 3 and 6. months of therapy, respectively (mean 8.85. months, range 6. days-18.4. months). Patients transitioned to GPB maintained excellent control of ammonia and glutamine levels. There were 36 HACs in 11 patients before GPB and 11 in 7 patients while on GPB, with a reduction from 2.98 to 0.88 episodes per year. Adverse events occurring in at least 10% of patients while on GPB were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash/papule. Conclusion: GPB was safe and effective in UCD patients aged 2. months to 2. years. GPB use was associated with good short- and long-term control of ammonia and glutamine levels, and the annualized frequency of hyperammonemic crises was lower during the study than before the study. There was no evidence for any previously unknown toxicity of GPB.

AB - Introduction: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2. months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. Methods: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2. months to 2. years were switched to, or started, GPB. Retrospective data up to 12. months pre-switch and prospective data during initiation of therapy were used as baseline measures. The primary efficacy endpoint of the integrated analysis was the successful transition to GPB with controlled ammonia (<. 100. μmol/L and no clinical symptoms). Secondary endpoints included glutamine and levels of other amino acids. Safety endpoints included adverse events, hyperammonemic crises (HACs), and growth and development. Results: 82% and 53% of patients completed 3 and 6. months of therapy, respectively (mean 8.85. months, range 6. days-18.4. months). Patients transitioned to GPB maintained excellent control of ammonia and glutamine levels. There were 36 HACs in 11 patients before GPB and 11 in 7 patients while on GPB, with a reduction from 2.98 to 0.88 episodes per year. Adverse events occurring in at least 10% of patients while on GPB were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash/papule. Conclusion: GPB was safe and effective in UCD patients aged 2. months to 2. years. GPB use was associated with good short- and long-term control of ammonia and glutamine levels, and the annualized frequency of hyperammonemic crises was lower during the study than before the study. There was no evidence for any previously unknown toxicity of GPB.

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KW - Infants

KW - Urea cycle disorders

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