Results from a Nationwide Cohort Temporary Utilization Authorization (ATU) Survey of Patients in France Treated with Pheburane® (Sodium Phenylbutyrate) Taste-Masked Granules

Abstract

ObjectivesThe aim of this study was to describe a nationwide system for pre-marketing follow-up (cohort temporary utilization authorization [ATU] protocol; i.e., ‘therapeutic utilization’) of a new taste-masked formulation of sodium phenylbutyrate (NaPB) granules (Pheburane®) in France and to analyze safety and efficacy in this treated cohort of patients with urea cycle disease (UCD).MethodsIn October 2012, a cohort ATU was established in France to monitor the use of Pheburane® on a named-patient basis. All treated UCD patients were included in a follow-up protocol developed by the Laboratory (Lucane Pharma) and the French Medicines Agency (ANSM), which recorded demographics, dosing characteristics of NaPB, concomitant medications, adverse events, and clinical outcome during the period of treatment. Following the granting of the Marketing Authorization in Europe, the cohort ATU was terminated approximately 1 year after its initiation, as the product was launched on the French market.ResultsThe ease of administration and acceptability were much better with the new taste-masked formulation than with the previous treatment. No episodes of metabolic decompensation were observed over a treatment period ranging from 3 to 11 months with Pheburane® and the range of ammonia and glutamine plasma levels improved and remained within the normal range. In all, no adverse events were reported with Pheburane® treatment.ConclusionsThe recently developed taste-masked formulation of NaPB granules improved the quality of life for UCD patients. This may translate into improved compliance, efficacy, and safety, which may be demonstrated either in further studies or in the post-marketing use of the product.

Endoplasmic Reticulum Stress Is Associated With Autophagy and Cardiomyocyte Remodeling in Experimental and Human Atrial Fibrillation

“…4,7 Therapeutic Implications From a translational perspective, the current results identify a potential benefit of pharmacological inhibition of ER stress as a therapeutic strategy in clinical AF. Among the available compounds, 4PBA seems promising, because this compound is already approved for clinical use to treat urea cycle disorders 36,37,71 and is available under the trade names Buphenyl (available in the United States since 1996) and Ammonaps (available in Europe since 1999). 4PBA acts as a chemical chaperone and alleviates ER stress by protecting from aggregation of misfolded proteins.…”

“…Tachypacing (TP) augments levels of endoplasmic reticulum (ER) stress markers and the autophagy gene ATG12. A, Representative Western blot of phosphorylated eIF2a S51 (molecular weight [MW], 38), an ER stress marker, basal eIF2a (MW,36), and GAPDH levels during normal pacing (NP) or in response to TP for the indicated duration. B, Quantified data of the ratio of phosphorylated eIF2a S51 normalized for basal eIF2a protein levels (N=3).…”

An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

“…In addition, due to the palatability issues associated with sodium phenylbutyrate, in recent years, the scientific community has been interested in the development of taste-masked granules of this pediatric drug which will be very useful to improve treatment adherence [109]. To date, two clinical trials have shown that the recently developed taste-masked formulation of sodium phenylbutyrate granules improves quality of life in patients with UCDs [110, 111]. …”

Averting the foul taste of pediatric medicines improves adherence and can be lifesaving – Pheburane® (sodium phenylbutyrate)

“…These results led the investigators to initiate the first French nationwide 1-year cohort study on 25 patients, of whom 21 were children 13. All of them suffered from UCD, and prior to introducing the taste-masked granule formulation of NaPB, all were maintained on another nitrous scavenger, either NaPB or sodium benzoate.…”