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

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.