sodium phenylbutyrate / Generic mfg. - LARVOL DELTA

Recurrent Hyperammonemic Encephalopathy Status Post Ureterosigmoidostomy (ACG 2026) - "Urine-stool cultures repeatedly grew E. coli , and episodes consistently resolved with lactulose and rifaximin...Episodes continued despite arginine and sodium phenylbutyrate supplementation...USO, a method of urinary diversion post cystectomy, is thought to cause extrahepatic encephalopathy via colonic exposure to urine and increased delivery of ammonia to the portal drainage system. Our case illustrates this rarely described anatomic cause of hyperammonemia, the morbidity that results, and definitive management by elimination of urinary-colonic contact."

CNS Disorders • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatic Encephalopathy • Hepatology • Immunology • Obesity

Safety, tolerability, and efficacy of RIPK1 inhibitor, SAR443820, in amyotrophic lateral sclerosis (HIMALAYA): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. (PubMed, Lancet Neurol) - P2 | "SAR443820 did not show clinical benefit and was associated with higher hepatic enzyme increase, indicating that further clinical development of SAR443820 in ALS is not warranted."

Clinical • Journal • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • RIPK1

Therapeutic Challenges and Future Breakthroughs in Amyotrophic Lateral Sclerosis: From Precision Medicine to Innovative Trial Design. (PubMed, Drug Des Devel Ther) - "These include the modest survival benefit of riluzole, the narrow eligible population for edaravone, and the complex trajectory of sodium phenylbutyrate-taurursodiol, which received accelerated approval but was subsequently voluntarily withdrawn after its confirmatory Phase III trial failed to meet its primary endpoints. Future success depends on establishing multimodal biomarker panels, implementing genetic testing-guided individualized therapy, developing combination regimens, and integrating patient-reported outcomes with palliative care. Although substantial challenges remain, the clinical success of Tofersen provides evidence that precision therapeutic strategies may gradually transform ALS management toward a more individualized and disease-modifying approach."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Inflammation • Palliative care

Neonatal-Onset Carbamoyl Phosphate Synthetase 1 Deficiency: Favorable Short-Term Outcome Following Early Aggressive Treatment (SSIEM 2026) - "Medical treatment included sodium benzoate, sodium phenylbutyrate, carglumic acid, and L-argi-nine...Early recognition and aggressive treatment, including extracorporeal ammonia removal and combined medical therapy, were associated with survival and favorable short-term neurological outcome. This case highlights the importance of rapid metabolic evaluation and timely intervention in neonates with hyperammonemia."

Infectious Disease • Metabolic Disorders • Septic Shock

Balancing Risk and Response: ACTH Therapy for Infantile Spasms in Citrullinemia Type I (SSIEM 2026) - "First-line treatment includes corticosteroids (CS), such as adrenocorticotropic hormone (ACTH), followed by vigabatrin...Intensive monitoring included frequent ammonia levels and daily plasma amino acids, with adjustments to diet (Cyclinex-1, breast milk, arginine) and sodium phenylbutyrate... Adrenocorticotropin can be safely administered in citrullinemia type I with intensive metabolic support and multidisciplinary care. This case challenges conventional contraindications and underscores the importance of individualized risk–benefit assessment in treating IS in UCD patients."

CNS Disorders • Endocrine Disorders • Epilepsy • Metabolic Disorders • Nephrology • ASS1

Metabolic cell competition in the glioblastoma tumour microenvironment: glucose, glutamine, and lactate as determinants of immune exclusion and targets for pharmacological reprogramming. (PubMed, Front Oncol) - "Glioblastoma (GBM) remains the most lethal primary brain tumour, with median overall survival of 14 to 16 months despite maximal safe surgical resection, concurrent chemoradiotherapy, and adjuvant temozolomide...Disrupting glucose and glutamine metabolism through glutamine antagonism (DON and prodrugs JHU083/JHU395), dichloroacetate (DCA)-mediated PDK inhibition, intravenous pharmacological ascorbate-mediated GAPDH inactivation and HIF-1alpha destabilisation, systemic glucose restriction (SGLT2 inhibitors), sodium phenylbutyrate-mediated glutamine depletion, and monocarboxylate transporter inhibition can invert this competitive hierarchy, reprogramming the immunosuppressive myeloid compartment while preserving T cell fitness; mebendazole is additionally reviewed as a multi-target anti-parasitic repurposing candidate with demonstrated GBM preclinical survival benefit...GBM cells and immunosuppressive myeloid cells are proposed to constitute a substrate-dependent..."

Journal • Review • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • GAPDH • HIF1A • NLRP3

Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=24 | Suspended | Sponsor: Jerry Vockley, MD, PhD | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Jun 2026 ➔ Jun 2028

Trial completion date • Trial primary completion date • Metabolic Disorders • Pediatrics

PORTAL HYPERTENSION AS THE DOMINANT FEATURE OF PIGM-RELATED GPI BIOSYNTHESIS DISORDER: A FAMILIAL CASE SERIES (ESPGHAN 2026) - "Further studies are needed to clarify the long-term impact of early sodium phenylbutyrate therapy. Contact e-mail address [email protected]"

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Hematological Disorders • Hepatology • Portal Hypertension • Thrombosis • CD55 • CD59 • GPI

Treatment strategies, radiological recovery, and neurodevelopmental outcomes in paediatric Maple Syrup Urine Disease: a 20-year single-centre experience from Türkiye. (PubMed, Metab Brain Dis) - "Evidence on long-term outcomes in paediatric cohorts, particularly with pharmacological adjuncts such as sodium phenylbutyrate (NaPBA) and radiological recovery, remains limited...A phenotype-specific approach combining early dietary intervention, timely haemodialysis in acute crises, and selective use of NaPBA may support metabolic stabilisation and radiological improvement in selected patients. Larger multicentre studies are warranted to validate these findings and refine management protocols."

Journal • Retrospective data • Developmental Disorders • Metabolic Disorders • Pediatrics

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

Diagnostic Dilemma: Acute Encephalopathy from Hyperammonemia in a Kidney-Pancreas Recipient (ATC 2026) - "Tacrolimus was switched to cyclosporine due to neurotoxicity concerns...Despite therapy with lactulose, rifaximin, and levocarnitine, hyperammonemia persisted, requiring hemodialysis...Later, sodium phenylbutyrate was discontinued.* Post-transplant hyperammonemia of unclear etiology caused recurrent encephalopathy in this SPK recipient but improved with sodium phenylbutyrate, allowing discontinuation of dialysis* Post-transplant hyperammonemia is a rare phenomenon that has been described most often in the lung transplant recipient population... Post-transplant hyperammonemia is a rare phenomenon that has been described most often in the lung transplant recipient population. Although hyperammonemia has been linked to calcineurin inhibitors in several lung transplant case reports, the mechanism remains largely unknown. Our patient had no clear reason for her hyperammonemia, although immunosuppression and biliary infection could have contributed."

Cardiovascular • Chronic Kidney Disease • CNS Disorders • Epilepsy • Fibrosis • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Sarcopenia • Thrombosis • Type 2 Diabetes Mellitus

Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. (PubMed, Ann Indian Acad Neurol) - "Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Efficacy of Sodium Phenylbutyrate-Taurursodiol in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. (PubMed, Ann Indian Acad Neurol) - "Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining."

Journal • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Amyotrophic Lateral Sclerosis: Therapeutic Innovations and Evolving Regulatory Approaches. (PubMed, CNS Neurol Disord Drug Targets) - "Despite extensive research, riluzole and edaravone remain the only globally approved disease-modifying therapies, offering modest survival benefits...The accelerated approval and subsequent withdrawal of sodium phenylbutyrate-taurursodiol (AMX0035) are discussed as a critical case study highlighting the challenges of regulatory flexibility in rare, fatal diseases. Advances in biomarker development, especially neurofilament light chain, are examined for their growing role in trial design and therapeutic evaluation. Collectively, these insights underscore a shift toward biomarker- informed and precision-based approaches that may improve future ALS therapeutic development."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Respiratory Diseases • NEFL

Phase II trial of sodium phenylbutyrate and taurursodiol in Wolfram syndrome. (PubMed, J Clin Invest) - "PB&TURSO was associated with improved or stabilized pancreatic function, vision, and overall symptom burden in individuals with Wolfram syndrome, a rare and progressive degenerative disease."

Journal • P2 data • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Nephrology

The Effects of Sodium Phenylbutyrate on Circulating Branched Chain Amino Acids (clinicaltrials.gov) - P=N/A | N=8 | Completed | Sponsor: University of Nottingham | Recruiting ➔ Completed

Trial completion • Obesity

NAPVAT: Na-Phenylbutyrate VAscular Trial (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: University of Pennsylvania | Trial completion date: Jan 2028 ➔ Jun 2029 | Trial primary completion date: Jan 2027 ➔ Jan 2028

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders

Developmental and Epileptic Encephalopathy due to Biallelic Pathogenic Variants in PIGM. (PubMed, Ann Clin Transl Neurol) - "Our findings establish PIGM as a causative gene of early-onset developmental and epileptic encephalopathy and expand the clinical and radiological spectrum of PIGM deficiency to include hypomyelination and prenatal onset. This study underscores the importance of including PIGM in the differential diagnosis of developmental and epileptic encephalopathy and leukoencephalopathies and provides further insight into the molecular mechanisms underlying phenotypic variability of GPI-anchor disorders."

Journal • Absence Seizure Disorder • Cardiovascular • CNS Disorders • Epilepsy • Hematological Disorders • Thrombosis

QbD-based, greenness and whiteness-assessed LC-MS/MS method for simultaneous determination of sodium phenylbutyrate and Taurursodiol with pharmacokinetic application. (PubMed, J Pharmacol Toxicol Methods) - "Greenness and whiteness assessment further demonstrated strong environmental compatibility. Overall, the developed LC-MS/MS protocol is precise, reproducible, and sustainable, providing a valuable tool for preclinical pharmacokinetic investigations of NaPB and TRS."

Journal • PK/PD data

Impaired VLCFA-peroxisome-mediated intestinal epithelial repair causes gastrointestinal sequelae of long COVID. (PubMed, Dev Cell) - "Importantly, the FDA-approved sodium phenylbutyrate (NaPB) and fenofibrate alleviate these symptoms by promoting peroxisome proliferation and restoring epithelial repair. These findings provide insights into the GI pathogenesis of long COVID and highlight the therapeutic potential of enhancing the VLCFA-PPAR-peroxisome axis to mitigate persistent GI complications."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Furthermore, the review examines emerging therapies at various stages, including clinical and pre-clinical development, such as glycerol/sodium phenylbutyrate, ornithine phenylacetate, fecal microbiota transplantation, engineered bacteria, liposome-supported peritoneal dialysis, GABAA receptor modulating steroid antagonists (GAMSA), activated carbon microspheres, and glutamine synthetase replacement. This review consolidates knowledge on HE, providing a comprehensive resource for clinicians, researchers, and healthcare professionals involved in managing this complex disorder. The synthesis of epidemiological data, pathophysiological insights, and therapeutic advancements offers a holistic view of HE, paving the way for improved diagnosis and targeted interventions."

Journal • Review • Cardiovascular • CNS Disorders • Heart Failure • Hepatic Encephalopathy • Transplantation

Short- and Long-Term Effects of Sodium Phenylbutyrate on White Matter and Sensorimotor and Cognitive Behavior in a Mild Murine Model of Encephalopathy of Prematurity. (PubMed, Int J Mol Sci) - "The second aim was to determine whether sodium phenylbutyrate (PBA), which is already prescribed in neonates for another indication, could prevent these disabilities. JH induced lasting dysmyelination in males, not prevented by PBA, contrary to the discrete JH-induced neurobehavioral deficits observed in both sexes in the short and long term."

Journal • Preclinical • Cardiovascular • CNS Disorders • Critical care • Developmental Disorders • Hematological Disorders • Psychiatry • Solid Tumor • Thrombosis

Sodium Phenylbutyrate Ameliorates Ovariectomy-Induced Bone Loss in Rats. (PubMed, Medicina (Kaunas)) - " SPB mitigates OVX-induced oxidative stress, inflammatory cytokine release, and osteoclast-mediated resorption, resulting in partial but significant improvements across biochemical, structural, and histomorphometric parameters in estrogen-deficient rats. Given its established clinical safety profile, SPB emerges as a cost-effective candidate for repurposing in postmenopausal osteoporosis, warranting further translational and clinical studies."

Biomarker • Journal • Preclinical • Osteoporosis • Rheumatology • CTSK • IL6 • TNFA

CRRT in Nonhepatic Hyperammonemic Encephalopathy After Roux-en-Y Gastric Bypass (KIDNEY WEEK 2025) - "After nutrient and vitamin supplementation, L-carnitine, arginine, sodium phenylbutyrate and lactulose, the arterial ammonia normalized within two weeks. Clinicians faced with a similar clinical case can consider dialysis as an initial therapy. Future research should focus on understanding the role of CRRT dose, timing, and modality in management of patients with hyperammonemia."

Bariatric surgery • Cardiovascular • CNS Disorders • Dermatitis • Dermatology • Epilepsy • Hematological Disorders • Hepatology • Hypertension • Immunology

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