Ravicti (glycerol phenylbutyrate) / Immedica, Amgen - LARVOL DELTA

A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Tongji Hospital | Initiation date: Sep 2025 ➔ Dec 2025

Trial initiation date • Metabolic Disorders

Glycerol Phenylbutyrate. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

Developing a Quantitative EEG-Based Biomarker for SLC6A1 Related Neurodevelopmental Disorder (AES 2025) - P1 | "We have developed a measure to detect SLC6A1-related seizures and used this to discriminate pre-treatment from post-medication EEGs. We are exploring additional features and testing which representation of delta power is most generalizable. This approach and the results show promise towards the goal of developing a biomarker for SLC6A1 treatment response."

Biomarker • Late-breaking abstract • Neurodevelopmental • CNS Disorders • Developmental Disorders • Epilepsy • Psychiatry

Phenylbutyrate for Dravet Syndrome (AES 2025) - P1 | "Glycerol phenylbutyrate is well-tolerated, but acidosis can lead to hospitalization in vulnerable children. The drug was associated with seizure frequency improvement (80% reduction) for one of six (17%) treated children with Dravet Syndrome due to SCN1A. This response rate is lower than observed for children with SLC6A1 (70%) and STXBP1 (60%)."

Anorexia • CNS Disorders • Epilepsy • Metabolic Disorders • XBP1

Urea cycle disorders in Argentina, analysis from a cohort of 135 patients diagnosed in the last 20 years. (SSIEM 2023) - "76% required chronic treatment: sodium benzoate 76%, sodium phenylbutyrate 27%, and glycerol phenylbutyrate 12%...The mortality rate was higher than the one reported in other countries. We reported their presenting symptoms and sociocultural characteristics as well as accessibility to diagnosis and treatment, trying to identify the negative correlations in order to portray which variables are most related to worse results."

Clinical • Metabolic Disorders

STXBP1-E: Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Weill Medical College of Cornell University | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Developmental Disorders • Epilepsy • Psychiatry • XBP1

PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS) (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Technical University of Munich | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Aug 2024 ➔ Mar 2026

Trial completion date • Trial primary completion date

PBA Use for Treatment of ATF6-/- Patients (clinicaltrials.gov) - P1 | N=2 | Suspended | Sponsor: Columbia University | Trial primary completion date: Aug 2025 ➔ Aug 2027

Trial primary completion date • Achromatopsia • Ophthalmology • ATF6

A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Tongji Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders

Clinical characteristics and long-term outcomes of 101 patients with urea cycle disorders in China. (PubMed, Orphanet J Rare Dis) - "This study is the first to describe the clinical features and long-term outcomes of UCDs in a large sample of Chinese patients, highlighting the importance of newborn screening for early diagnosis and improved treatment outcomes."

Journal • Genetic Disorders • Metabolic Disorders

PBA Use for Treatment of ATF6-/- Patients (clinicaltrials.gov) - P1 | N=2 | Suspended | Sponsor: Columbia University | Trial completion date: May 2027 ➔ Aug 2027 | Not yet recruiting ➔ Suspended | Trial primary completion date: May 2027 ➔ Aug 2025

Trial completion date • Trial primary completion date • Trial suspension • Achromatopsia • Ophthalmology • ATF6

Correction of a Traffic-Defective Missense ABCB11 Variant Responsible for Progressive Familial Intrahepatic Cholestasis Type 2. (PubMed, Int J Mol Sci) - "GPB, PA, ursodeoxycholic acid (UDCA), alone or in combination with 4-PB, suberoylanilide hydroxamic acid (SAHA), C18, VX-445, and/or VX-661, significantly corrected both the traffic and the activity of Abcb11R1128C. Such correctors could represent new pharmacological insights for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the transporter's traffic."

Journal • Cholestasis • Hepatology • ABCB1

Cerebral Edema Due to Hyperammonemia: A Case of Suspected Urea Cycle Disorder in Adult Patient (ATS 2025) - "The patient was dialyzed for hyperammonemia, treated with hypertonic saline for cerebral edema, and managed for seizures with levetiracetam, lacosamide, and topiramate...This can then be followed by outpatient amino acid supplementation, dietary protein restriction, in some cases, nitrogen scavenger therapy (such as sodium phenylbutyrate or glycerol phenylbutyrate) and avoidance of medications that raise ammonia levels, such as valproic acid in our patient. Mild cases of UCDs can present in adults during physiologic distress, requiring high suspicion as delays may lead to irreversible cerebral injury or death. In patients with unclear neurologic symptoms, particularly new-onset seizures or cerebral edema checking ammonia levels is crucial for prompt identification and treatment."

Clinical • CNS Disorders • Epilepsy • Metabolic Disorders • Pediatrics • Psychiatry • Schizophrenia

LC-MS/MS and LC-PDA Methods for Robust Determination of Glycerol Phenylbutyrate in Biological Fluids and High-Resolution Mass Spectrometric Identification of Forced Degradation Product and Its Whiteness. (PubMed, ACS Omega) - "Moreover, in forced degradation experiments, the active substance was unstable in acid, alkali, and oxide conditions, and an elimination reaction forms the novel degradation product. Lastly, the method was evaluated to have excellent whiteness, efficiency, and practicality, making it suitable for application in all analytical method development laboratories."

Journal • Metabolic Disorders

Glutamine and Hypoxic Brain Injury: A Mechanistic Insight. (PAS 2025) - "Hypoxia resulted in significant metabolic acidosis, cerebral lactic acidosis, and cerebral edema (Table 1). Hypoxic piglets reoxygenated for 4 hours with or without HT had increased GLN, but decreased GLU in their CC compared to controls (Figure 1). Astrocytes incubated in GLN had an increased number of cellular processes indicative of activated astrocyte morphology."

Anesthesia • CNS Disorders • Metabolic Disorders • Vascular Neurology

Clinical Study on the Treatment of STXBP1 Gene-related Encephalopathy with Glycerol Phenylbutyrate (ChiCTR) - P=N/A | N=13 | Not yet recruiting | Sponsor: Hunan Children‘’s Hosptial; Hunan Children‘’s Hosptial

New trial • CNS Disorders • Developmental Disorders • Psychiatry • XBP1

A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders (clinicaltrials.gov) - P=N/A | N=40 | Not yet recruiting | Sponsor: Tongji Hospital

New trial • Metabolic Disorders

PDH-RAVICTI: A Phase II, Multicentric, Prospective, Non-comparative Clinical Trial to Assess the Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency (PDH) Patients with Glycerol Phenybutyrate (RAVICTI®) (clinicaltrials.gov) - P2 | N=15 | Not yet recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris

New P2 trial • Metabolic Disorders

Perspectives on long-term medical management of urea cycle disorders: insights from a survey of UK healthcare professionals. (PubMed, Orphanet J Rare Dis) - "To standardise the treatment of UCDs within and between metabolic centres in the UK, there is merit in developing a UK-specific treatment guideline."

Journal • Metabolic Disorders

4-Phenylbutyrate restored GABA uptake, mitigated seizures in SLC6A1 and SLC6A11 microdeletions/3p- syndrome: From cellular models to human patients. (PubMed, Epilepsy Res) - P1 | "Haploinsufficiency of SLC6A1 and SLC6A11 contributes to the epileptic phenotypes observed in 3p- syndrome, marking this as the first study to biochemically characterize the functional impact of these deletions. Treatment with PBA may provide therapeutic benefits, particularly for addressing seizures and motor deficits, though further exploration of PBA's long-term effects in patients with 3p- syndrome is warranted."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Pediatrics

Single centre retrospective review of plasma branched-chain amino acid levels in children with urea cycle disorders: Impact of treatment modalities and disease severity. (PubMed, Mol Genet Metab Rep) - "Scavenger treatment groups comprised sodium benzoate (NaBz, n = 20), sodium phenylbutyrate (NaPBA, n = 5), NaBz+NaPBA (n = 14), and a control group receiving neither NaBz nor NaPBA (n = 14)...We speculate that individuals with greater disease severity may be prone to BCAA deficiency, caused by BCAA consumption when alternative urea disposal pathways are used. Practical reflections on our audit were that to increase the proportion of plasma BCAA levels in the normal range, we needed to alter the biological value of protein intake, prescribe higher doses of scavenger to facilitate safe levels of protein intake, and give EAA supplements if indicated."

Journal • Retrospective data • Metabolic Disorders

STXBP1-E: Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1 | N=50 | Enrolling by invitation | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Jan 2025 ➔ Dec 2025

Trial primary completion date • CNS Disorders • Developmental Disorders • Epilepsy • Psychiatry • XBP1

PBA Use for Treatment of ATF6-/- Patients (clinicaltrials.gov) - P1 | N=2 | Not yet recruiting | Sponsor: Columbia University | Trial completion date: May 2025 ➔ May 2027 | Trial primary completion date: May 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Achromatopsia • Ophthalmology • ATF6

Mechanistic Insights into Pharmacological Interventions for SLC6A1 Variant-related Disorders (AES 2024) - "The reduction in GABA reuptake likely contributes to the observed phenotypes in patients with SLC6A1 variant-related disorders, including epilepsy, neurodevelopmental delay, and autism spectrum disorder. These findings suggest that the pharmacological agents tested may offer viable therapeutic options. Ravicti (glycerol-phenylbutyrate) is currently in clinical trials for SLC6A1-related disorders, but this study aims to tease out mechanisms to identify alternative therapeutic treatments."

Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Mood Disorders • Psychiatry

Phenylbutyrate for syngap1-related Developmental and Epileptic Encephalopathy (AES 2024) - "Glycerol phenylbutyrate is a promising novel therapy for children with SYNGAP1. In ongoing work, we are (1) reviewing developmental assessment data and (2) enrolling additional children with SYNGAP1 and other monogenetic developmental and epileptic encephalopathies."

CNS Disorders • Epilepsy • Hematological Disorders • Metabolic Disorders • XBP1