glycerol phenylbutyrate / Generic mfg. - LARVOL DELTA

Glycerol Phenylbutyrate Treatment in a Pediatric Cohort of SLC6A1-Related Neurodevelopmental Disorder. (PubMed, Pediatr Neurol) - "Glycerol phenylbutyrate treatment is relatively well tolerated, and although it is effective in reducing the frequency of seizures and improving video-electroencephalogram abnormalities, it is less effective in ameliorating cognitive and psychiatric manifestations."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Metabolic Disorders • Movement Disorders • Pediatrics • Psychiatry

Drug repurposing of glycerol phenylbutyrate for children with SLC6A1-related neurodevelopmental disorder: A prospective open-label case series. (PubMed, Mol Genet Metab) - "Glycerol phenylbutyrate was associated with improvements in individualized outcomes in children with SLC6A1-NDD. However, personalized goal attainment measures are susceptible to expectation and observer bias in open-label study designs. Controlled studies are needed to determine efficacy and guide patient selection."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Pediatrics • Psychiatry • Rare Diseases

Phenylbutyrate-Responsive SLC6A1-Related Neurodevelopmental Disorder Associated With a Familial Variant. (PubMed, J Child Neurol) - "Because of persistent seizures despite antiseizure medications, glycerol phenylbutyrate (GPB), a prodrug of 4-PBA, was initiated, resulting in complete seizure freedom and reduction of epileptiform discharges on follow-up electroencephalography. These findings highlight the potential role of genotype-informed precision therapy in SLC6A1-related disorders and underscore the importance of careful variant interpretation in familial cases."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Psychiatry

PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS) (clinicaltrials.gov) - P2 | N=32 | Completed | Sponsor: Technical University of Munich | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Aug 2026 | Trial primary completion date: Mar 2026 ➔ Aug 2026

Trial completion • Trial completion date • Trial primary completion date

Targeted Branched Chain Amino Acid Supplementation Corrects Persistent Deficiency in Urea Cycle Disorders: Five Year Longitudinal Analysis (SSIEM 2026) - "Conclusion BCAA deficiency is high across UCD's, particularly in ASA and Cit, with leucine deficiency common in OTC and HHH. Targeted BCAA supplementation effectively restores plasma concentrations and offers a flexible, alternative to full EAA mixtures."

Genetic Disorders • Metabolic Disorders

Partnering with our Patients to Repurpose Drugs: Glycerol Phenylbutyrate Effective in Children with SLC6A1-Neurodevelopmental Disorder (SSIEM 2026) - "In this small case series, experimental treatment with glycerol phenylbutyrate appeared safe and was associated with meaningful improvements in personalized goals and seizure control. The use of GAS proved essential for capturing heterogeneous but clinically relevant outcomes in this rare population. These findings support the potential for GPB as a targeted therapy for SLC6A1-NDD, though blinded, randomized controlled trials (such as n-of-1 designs) are required to rule out placebo effects and the natural disease course."

Clinical • Neurodevelopmental • Ataxia • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Movement Disorders • Psychiatry

Bridging the Treatment Gap: A Systematic 10-Principle Framework for Drug Repurposing in Inherited Metabolic Diseases (SSIEM 2026) - " We report our experience with this framework applied in Emma CPM across several conditions: ACO2 Deficiency: Triheptanoin showed potential in restoring mitochondrial energy flux and neurologic status...MT-ATP6 & SURF1-def: Sildenafil was utilized to modulate mitochondrial biogenesis and improve clinical stabilization in Leigh syndrome spectrum disorders... The ECPM framework demonstrates that drug repurposing for IMDs is most effective when personalized biological validation meets innovative trial methodology. By prioritizing "what matters to the patient" through GAS and PROMs, we generate higher level evidence even in small patient numbers. This 10-principle systematic approach provides a scalable model for the global rare disease community to accelerate the delivery of precision therapies."

CNS Disorders • Epilepsy • Metabolic Disorders • Rare Diseases • GRIN2B

Contrasting Impacts of Two ABCB11 Variants Affecting the Same Residue in Progressive Familial Intrahepatic Cholestasis Type 2. (PubMed, Am J Physiol Gastrointest Liver Physiol) - "In vitro, ursodeoxycholic acid combined with glycerol phenylbutyrate increased ABCB11T463P canalicular expression (40.2 ± 7.7% of the wild-type, p <0.0001) and improved transport activity (32.4 ± 10.3% of the wild-type, p <0.0001). VX-770 and SBC040 increased ABCB11T463I function from 37.9 ± 2.5% (DMSO) to 73.2 ± 12.3% and 76.1 ± 17.5%, respectively, of the wild-type activity (p <0.0001). ABCB11 missense variations, even affecting the same residue, can cause various molecular defects, resulting in mild to severe phenotypes. 3D structure and in vitro analyses could be used to predict the severity of missense variants and guide the treatment of PFIC2 patients with pharmacological modulators."

Journal • Cholestasis • Hepatology • Transplantation • ABCB1

Biochemical testing and pathology reveal rare cause of pediatric acute liver failure: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. (PubMed, JPGN Rep) - "This case contributes to our growing understanding of the phenotypic presentation of HHH, a rare genetic cause of liver failure not included on newborn screening but with specific treatment implications. We also highlight the importance of collecting biochemical genetics labs and liver biopsy early in the disease course and discuss how a patient's voluntary self-restriction of protein can offer helpful clues in the diagnostic evaluation."

Journal • Ataxia • CNS Disorders • Epilepsy • Hepatology • Liver Failure • Metabolic Disorders • Movement Disorders • Pediatrics

Study protocol: double-blind, randomized, prospective, placebo controlled parallel group phase II study to investigate the effect of glycerol phenylbutyrate (GPB) on neurofilament light chain (NfL) levels in patients with corticobasal syndrome (CBS). (PubMed, Neurol Res Pract) - P2 | "If successful, this clinical trial could identify a novel therapeutic approach for slowing disease progression in CBS, contributing to a broader understanding of GPB's therapeutic potential."

Journal • P2 data • CNS Disorders • NEFL

Pre-emptive treatment in later-onset urea cycle disorders: a clinical perspective on glycerol phenylbutyrate. (PubMed, Orphanet J Rare Dis) - "We suggest that a proactive treatment strategy may reduce the risk of neurological complications in selected patients with later-onset UCD. We propose a shift from reactive to pre-emptive management, positioning GPB as a potential tool in this context."

Journal • Review • Metabolic Disorders

Long-Term Efficacy and Safety of Glycerol Phenylbutyrate in Japanese Patients With Urea Cycle Disorders: Results From a Phase 3 Switch-Over and 12-Month Extension Study. (PubMed, JIMD Rep) - "Sodium phenylbutyrate (NaPBA) is used for nitrogen scavenging in urea cycle disorders (UCDs), but its volume, palatability, and sodium load affect adherence and ammonia control...It offers a practical and clinically advantageous alternative to NaPBA, extending previous evidence to Japanese individuals with UCDs. Trial registration: jRCT2071220110."

Journal • P3 data • Metabolic Disorders • Rare Diseases

Synthesis and preliminary enzymatic evaluation of polyol-based 4-phenylbutyrate derivatives. (PubMed, Bioorg Med Chem Lett) - "This compound exhibited significantly slower hydrolysis than glycerol phenylbutyrate, suggesting a sustained-release profile. In contrast, the erythritol derivative, due to its highly crystalline nature, failed to form an enzyme-accessible phase in simulated intestinal fluid, precluding enzymatic evaluation and indicating a potential dissolution-limited release mechanism."

Journal • Metabolic Disorders • Oncology

Unraveling 4-Phenylbutyrate's Therapeutic Role in SLC6A1 Disorders: Pharmacochaperoning Over HDAC Inhibition. (PubMed, Ann Clin Transl Neurol) - P1 | "PBA acts as a pharmacochaperone, not an HDAC inhibitor, to restore GAT-1 function and reduce seizure burden in the diseased mice, supporting pharmacochaperoning as the major mechanism for rescuing SLC6A1-related disorders."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders

Lupin Limited has announced that it has received approval from the United States Food and Drug Administration (USFDA) for its Abbreviated New Drug Application (ANDA) for Glycerol Phenylbutyrate Oral Liquid, 1.1 grams per mL, marking another addition to its US generics portfolio. (Business Upturn) - "The medication is indicated for the chronic management of patients with urea cycle disorders (UCDs), a rare condition that requires long-term therapeutic intervention."

ANDA • Metabolic Disorders

Ornithine Transcarbamylase Deficiency: An Unusual Cause of Hyperammonemia (NKF-SCM 2026) - "The patient was given lorazepam, and Pediatric Genetics was contacted...Renal replacement therapy is indicated if a patient does not respond to conservative measures or develops volume overload from fluid resuscitation. OTC deficiency must be considered in adult patients who develop acute hyperammonemia without liver failure."

Ataxia • CNS Disorders • Epilepsy • Genetic Disorders • Hepatology • Liver Failure • Metabolic Disorders • Movement Disorders

Impact of long-term nitrogen scavenger therapy on clinical outcome in individuals with urea cycle disorders. (PubMed, Sci Rep) - "No overall superiority among existing nitrogen scavenging agents with regard to the individual's metabolic stability, linear growth impairment and poor neurocognitive outcome was observed. Novel therapeutic strategies are urgently needed to ultimately improve health outcomes in individuals with UCDs in order to sufficiently meet guideline-specific goals."

Clinical data • Journal • Genetic Disorders • Metabolic Disorders • ASS1

PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS) (clinicaltrials.gov) - P2 | N=32 | Active, not recruiting | Sponsor: Technical University of Munich | Recruiting ➔ Active, not recruiting

Enrollment closed

At-home ammonia breath test for monitoring patients with a Urea Cycle Disorder (ACMG 2026) - "The at-home ammonia breath test system being developed by Enhance Diagnostics offers a practical, non-invasive method for real-time monitoring of metabolic status in UCD patients, with the potential to replace or reduce the need for invasive blood tests and emergency clinical visits. By providing accurate, quantitative insights into ammonia levels, the platform empowers patients and caregivers to make informed decisions, avoid unnecessary healthcare utilization, and facilitate prompt intervention when needed. Future work will focus on refining device design, completing verification and validation testing including an expanded clinical study, and pursuing FDA clearance prior to market launch in late 2026."

Clinical • Metabolic Disorders

ALDH18A1-related hyperammonemia with lactic acidosis (ACMG 2026) - "This case highlights the importance of periodic genome re-analysis and reporting heterozygous variants in patients with suspected IEM. Monitoring glutamine and glutamate is essential because they are both upstream sources for ornithine synthesis and downstream substrates for ammonia metabolism."

Atopic Dermatitis • Dermatology • Hematological Disorders • Immunology • Metabolic Disorders

Impact of glycerol phenylbutyrate on biochemistry and outcomes in paediatric patients with urea cycle disorders: a multicentre case series from Saudi Arabia. (PubMed, Orphanet J Rare Dis) - No abstract available

Journal • Metabolic Disorders • Pediatrics

STXBP1-E: Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Weill Medical College of Cornell University | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

PDH-RAVICTI: Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency Patients With Glycerol Phenylbutyrate (RAVICTI) (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial completion date: Dec 2026 ➔ Apr 2027 | Initiation date: May 2025 ➔ Oct 2025 | Trial primary completion date: Nov 2025 ➔ Mar 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Metabolic Disorders • DLAT • PDHA1

A Mysterious Case of Recurrent Confusion: An Unusual Presentation of Congenital Intrahepatic Portosystemic Shunt. (PubMed, Cureus) - "Due to multiple comorbidities, the patient was deemed unsuitable for shunt closure or liver transplantation but responded well to medical therapy with lactulose, rifaximin, sodium benzoate, glycerol phenylbutyrate, and L-ornithine L-aspartate, with no further episodes of encephalopathy on follow-up. This case underscores the importance of considering CPSS in adults presenting with hyperammonaemia and altered mental status in the absence of hepatic disease. Early recognition and multidisciplinary management are key to preventing recurrence and optimising outcomes."

Journal • Cardiovascular • CNS Disorders • Hepatic Encephalopathy • Hepatology • Transplantation

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