sodium phenylbutyrate / Generic mfg. - LARVOL DELTA

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

Sodium Phenylbutyrate as Therapeutics (SSIEM 2023) - No abstract available

Zevra Reports Third Quarter 2025 Financial Results and Corporate Update (The Manila Times) - "MIPLYFFA: Eight prescription enrollment forms during Q3 2025, bringing the total since product launch to 137; OLPRUVA: One prescription enrollment form during Q3 2025, bringing the total since product launch to 30...$26.1 million for Q3 2025, which includes $22.4 million of MIPLYFFA net revenue, $0.1 million of OLPRUVA net revenue, $2.4 million in net reimbursements from the French EAP for arimoclomol..."

Commercial • Genetic Disorders

CircSipa1l1 modulates melanoma cell differentiation by activating the IGF2BP1-ARHGDIB axis and ERK signaling pathway. (PubMed, J Transl Med) - "Our findings reveal that circSipa1l1 acts as an oncogenic circRNA by regulating the IGF2BP1/ARHGDIB/ERK axis in melanoma, suggesting it could be a potential therapeutic target for melanoma differentiation therapy."

Journal • Melanoma • Oncology • Solid Tumor • ARHGDIB • IGF2BP1 • Tyrosinase

Design, Synthesis, Development, and Biological Evaluation of Third-Generation Tubulin Inhibitors for Treatment of Cancer. (PubMed, Curr Protoc) - "The tubulin inhibitors have been synthesized in high yields without incorporating tubuvaline and tubuphenylalanine fragments present in the natural tubulysins, which are known to be essential for their anticancer activity.."

Journal • Oncology

Adverse drug reaction profiles of histone deacetylase inhibitors. (PubMed, Sci Rep) - "This study aimed to explore the global observational adverse drug reaction (ADR) profiles of the HDACIs: vorinostat, belinostat, panobinostat, pracinostat, entinostat, romidepsin, bufexamac and sodium phenylbutyrate. Thrombocytopenia observed with vorinostat, panobinostat and romidepsin may stem from dual inhibition of HDAC1 and HDAC2 and their higher volume of distributions (Vd). Despite all HDACIs having a similar mechanism of action, their unique pharmacology and differing physicochemical and pharmacokinetic properties landscape results in varying ADR profiles."

Adverse drug reaction • Journal • CNS Disorders • Depression • Hematological Disorders • Musculoskeletal Diseases • Psychiatry • Thrombocytopenia • HDAC1 • HDAC2 • HDAC3 • HDAC4 • HDAC9

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 | Recruiting ➔ Suspended

Trial suspension • Metabolic Disorders • Pediatrics

Real-World Clinical Experience With Sodium Phenylbutyrate and Taurursodiol at a Single Amyotrophic Lateral Sclerosis Center in the United States. (PubMed, Eur J Neurol) - "Experience in real-world clinical settings can help supplement trial data with information on the drug performance at various stages of disease progression. Adverse events impacted treatment persistence in routine clinical practice, underscoring the need for vigilant monitoring and tailored supportive interventions to optimize treatment adherence."

Journal • Real-world evidence • Retrospective data • Amyotrophic Lateral Sclerosis • CNS Disorders

Perioperative Management of a Patient With Arginase 1 Deficiency Undergoing a Liver Transplant: A Case Report. (PubMed, A A Pract) - "The primary management goals are to (1) reduce the risk for hyperammonemia by administering sodium phenylbutyrate and sodium benzoate to promote nitrogen excretion and (2) prevent catabolism by infusing carbohydrates and lipids. Vigilant monitoring for sodium derangements is necessary because these infusions may lead to hyper- or hyponatremia."

Journal • Cardiovascular • Heart Failure • Metabolic Disorders • Transplantation

An Individual Patient, Open Label Study to Use ACER-001 to Treat Combined D,L-2 Hydroxyglutaric Aciduria (C-2HGA) (clinicaltrials.gov) - P1 | N=1 | Enrolling by invitation | Sponsor: Jerry Vockley, MD, PhD

New P1 trial

Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Pediatric and Adults Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Jerry Vockley, MD, PhD | Trial completion date: Feb 2027 ➔ Jul 2027

Trial completion date • Metabolic Disorders • Pediatrics

Design, Synthesis, and Cytotoxic Evaluation of New Structurally Simplified and Highly Potent Third-Generation Tubulysin Derivatives. (PubMed, Chemistry) - "These inhibitors are devoid of tubuvaline and tubuphenylalanine fragments previously considered essential for tubulin inhibition activity...The method enables the synthesis of potent tubulin inhibitors by avoiding multistep synthetic and purification procedures, supporting the inhibitor's applicability for large-scale synthesis and potential therapeutic development. The structural modifications at the N-terminal result in the loss of activity from nM to µM range, whereas the C-terminal modification had minimal impact on the potency."

Journal • Cervical Cancer • Oncology • Solid Tumor

NAPVAT: Na-Phenylbutyrate VAscular Trial (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: University of Pennsylvania | Initiation date: May 2025 ➔ Dec 2025

Trial initiation date • Diabetes • Metabolic Disorders

Repurposing the memory-promoting meclofenoxate hydrochloride as a treatment for Parkinson's disease through integrative multi-omics analysis. (PubMed, NPJ Parkinsons Dis) - "Among these, meclofenoxate hydrochloride (MH) and sodium phenylbutyrate (SP) are indicated to be able to prevent mitochondrial destruction, reduce lipid peroxidation, and protect dopamine synthesis...The interaction of MH with a PD-related protein, sigma1, was confirmed experimentally. Thus, our findings support that MH potentially ameliorates PD by interacting with sigma1."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

A clinical efficacy study of Sodium phenylbutyrate in the treatment of diminished ovarian reserve (ChiCTR) - P=N/A | N=20 | Not yet recruiting | Sponsor: Zhongshan Hospital, Fudan University; Zhongshan Hospital, Fudan University

New trial

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

Estimating the Effect of a Discontinued Amyotrophic Lateral Sclerosis Treatment on Time-to-Death Using Sequential Target Trial Emulation (ISPOR 2025) - "OBJECTIVES: A combination product of sodium phenylbutyrate and taurursodiol (SP-T) was FDA-approved for amyotrophic lateral sclerosis (ALS) treatment in September 2022, then later withdrawn in April 2024, following unfavorable Phase 3 trial results... Using the Komodo Research Dataset, a claims database with mortality data, we implemented the target trial framework to emulate a sequence of hypothetical randomized trials comparing SP-T initiators vs non-initiators (standard care [riluzole or edaravone]) in each calendar month from October 2022 to March 2024 to estimate the observational analog of the intention-to-treat effect... We utilized a sequential target trial emulation to improve statistical efficiency in estimating the effect of SP-T initiation on time-to-death. Our results suggest a lower risk for death for ALS patients who initiated SP-T compared with non-initiators."

Amyotrophic Lateral Sclerosis • CNS Disorders