Loargys (pegzilarginase) / Spyre Therap, Immedica - LARVOL DELTA

Arginase Deficiency Presenting with Gait Disturbance: Diagnostic Challenge and Early Outcomes After Liver Transplantation (SSIEM 2026) - "As access to pegzilarginase therapy was not feasible, liver transplantation was planned as definitive treatment, and the patient underwent living donor liver transplantation at 4 years of age... This case highlights the diagnostic challenge of ARG1 deficiency, particularly in patients presenting with progressive gait disturbance without overt hyper-ammonemia. Plasma amino acid analysis is essential for early diagnosis. Liver transplantation appears to be an effective metabolic intervention; however, current evidence remains limited."

Genetic Disorders • Hematological Disorders • Metabolic Disorders • Transplantation

Pegzilarginase Bridges to Liver Transplant by Dissociating Arginine Neurotoxicity from Glutamine-Driven Ureagenesis in Arginase1 Deficiency (SSIEM 2026) - "While pegzilarginase (recombinant human arginase 1) effectively lowers plasma arginine, its specific impact on total ureagenesis capacity—notably glutamine levels and protein tolerance—remains a distinct clinical question. This case demonstrates that neurological stabilization and symptom reversal in ARG1-D are driven by the correction of arginine and its metabolites, independent of glutamine levels. While pegzilarginase serves as a highly effective biochemical bridge to reverse neurological decline, liver transplantation remains the only intervention to restore endogenous ureagenic capacity and provide complete dietary protein tolerance."

Movement Disorders • Transplantation • ARG1

A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With AML or MDS (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Immedica Pharma AB | Phase classification: P2 ➔ P1

Phase classification • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=76 | Completed | Sponsor: Immedica Pharma AB | Phase classification: P1/2 ➔ P1

First-in-human • Phase classification • Lung Cancer • Melanoma • Oncology • Small Cell Lung Cancer • Solid Tumor • BRAF

Relationship between elevated arginine and pathophysiology of progressive disease in arginase 1 deficiency. (PubMed, Mol Genet Metab) - "Chronic neurotoxicity from elevated arginine and its derivatives drives the progressive neurological decline in ARG1-D. Until recently, liver transplantation was the only intervention to halt progression of the disease, but it is not available to the majority of patients, is high risk, and resource intensive. In recently conducted clinical studies, enzyme therapy with pegzilarginase has demonstrated substantial reductions in arginine and its derivatives with improved clinical outcomes."

Journal • Review • CNS Disorders • Cognitive Disorders • Epilepsy • Metabolic Disorders • Movement Disorders • Solid Tumor • Transplantation

Efficacy and safety of pegzilarginase in patients below 2 years of age with arginase 1 deficiency: a phase 3, open-label, multi-centre study. (PubMed, EClinicalMedicine) - P3 | "In patients with ARG1-D <2 years of age, pegzilarginase demonstrated pharmacokinetic and pharmacodynamic responses comparable to older children and a favourable safety profile. Immedica Pharma AB."

Journal • P3 data • Metabolic Disorders • Movement Disorders • Pediatrics • Rare Diseases

LOARGYS (pegzilarginase-nbln). (PubMed, Clin Ther) - No abstract available

Journal

CLEAR: Evaluation of the Safety of Loargys Arginine Test System in Loargys-treated Patients (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Immedica Pharma US Inc

New trial

Rapid Detection of l-Arginine Using a Fluorescent Bacillus caldovelox Arginase for Monitoring Arginase Deficiency. (PubMed, Anal Chem) - "Patients with arginase deficiency require lifelong treatment with pegzilarginase and regular monitoring of blood l-arginine (l-Arg) levels...When applied to detect 200 or 400 μM l-Arg in fetal bovine serum to mimic the condition of arginase deficiency, the results closely matched those obtained using mass spectrometry. This study presents a rapid, simple, and specific fluorescent biosensor, offering a practical solution for patients with arginase deficiency to monitor their l-Arg levels routinely."

Journal

U.S. FDA has granted accelerated approval of Loargys (pegzilarginase-nbln) for the treatment of hyperargininemia in patients 2 years and older with Arginase 1 Deficiency (ARG1-D) (PRNewswire) - "This indication is approved under accelerated approval based on reduction of plasma arginine. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial....FDA accelerated approval of LOARGYS is based on positive results from the Phase 3 PEACE trial where LOARGYS significantly reduced plasma arginine from baseline compared to placebo at 24 weeks."

Accelerated approval • FDA approval • Genetic Disorders • Metabolic Disorders • Rare Diseases

Clinical Characteristics of Arginase 1 Deficiency: Natural History Insights From International Clinical Trials. (PubMed, J Inherit Metab Dis) - "The clinical development programme of pegzilarginase, a recombinant human ARG1 enzyme therapy, provides an opportunity to study the largest ARG1-D cohort to date...ARG1-D presents with a heterogeneous array of progressive and debilitating neurologic symptoms. These findings reflect the progressive impact of the disease and offer insights into its burden and natural history based on a large cohort, assessed using standardised neuromotor, cognitive, and quality-of-life instruments across international sites."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Metabolic Disorders • Movement Disorders • Pediatrics

Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency (clinicaltrials.gov) - P3 | N=3 | Completed | Sponsor: Immedica Pharma AB | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jun 2025

Trial completion • Trial completion date

Pegzilarginase demonstrates long-term, clinically meaningful improvements in functional mobility in ARG1-D: patient-level analysis from the Phase 3 PEACE trial (SSIEM 2023) - P3 | "ARG1-D is characterized by progressive mobility impairment despite current management. Pegzilarginase led to clinically meaningful functional mobility improvements in individual patients. These responses were maintained and further improved through 2 years of treatment."

Clinical • P3 data

Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency (clinicaltrials.gov) - P3 | N=3 | Active, not recruiting | Sponsor: Immedica Pharma AB | Trial completion date: Dec 2025 ➔ Oct 2025

Trial completion date

Long-Term Efficacy and Tolerability of Pegzilarginase in Arginase 1 Deficiency: Results of Two International Multicentre Open-Label Extension Studies. (PubMed, J Inherit Metab Dis) - "Most adverse events were mild/moderate; no treatment-related discontinuations or persistent antibodies occurred. Pegzilarginase produced sustained improvements in mobility, spasticity and biochemical control, supporting early intervention, long-term use and disease modification in ARG1-D."

Journal • Cognitive Disorders • Metabolic Disorders • Movement Disorders

Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency (clinicaltrials.gov) - P3 | N=3 | Active, not recruiting | Sponsor: Immedica Pharma AB | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2025 ➔ Jun 2025

Enrollment closed • Trial primary completion date

Arginase 1 deficiency: a treatable form of spastic paraplegia. (PubMed, Neurol Sci) - "Experts stress the importance of increased awareness of ARG1-D characteristics, noting that early recognition and treatment are crucial to patient outcomes. Greater recognition of ARG1-D's distinctive features, differential diagnosis, and diagnostic tools, even among non-specialist clinicians, could help prevent misdiagnoses and facilitate the identification of this rare yet treatable condition."

Journal • Review • Alzheimer's Disease • Cerebral Palsy • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Metabolic Disorders • Movement Disorders

Retrospective analysis of arginase 1 deficiency progression in adults over 5 years at a single metabolic centre. (PubMed, JIMD Rep) - "ARG1-D presents significant lifelong challenges with deteriorating mobility and more frequent metabolic crises. Current management strategies are insufficient for preventing progression, highlighting the need for innovative treatments like enzyme replacement and gene therapy."

Journal • Retrospective data • Gene Therapies • Metabolic Disorders • ARG1

Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency (clinicaltrials.gov) - P3 | N=3 | Recruiting | Sponsor: Immedica Pharma AB | Not yet recruiting ➔ Recruiting

Enrollment open

Experience with pegzilarginase outside clinical trial setting (SSIEM 2024) - "Sponsored by IMMEDICA PHARMA."

Clinical

Efficacy and safety of pegzilarginase in ARG1-D: PEACE study (SSIEM 2024) - "Sponsored by IMMEDICA PHARMA."

Clinical

ARGINASE-1 DEFICIENCY: ΑN INBORN ERROR OF METABOLISM AS A RARE CAUSE OF DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY (SSIEM 2024) - "At 22 y/o, seizures reappeared with generalized tonic-clonic spasms with initiation of combination of levetiracetam, clobazam and phenytoin, with poor seizure control...The enzyme replacement therapy, pegzilarginase, is the first possible disease-modifying therapy of the disease. Early diagnosis is of importance as it is a treatable cause of DEE. Palavras-chave : Arginase-1 deficiency, Urea cycle disorders, Developmental and epileptic encephalopathy, Metabolic epilepsy, Inborn errors of metabolism"

CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Metabolic Disorders • Movement Disorders

IMPROVED CLINICALLY MEANINGFUL TREATMENT OUTCOMES OF PEGZILARGINASE DURING LONGER-TERM TREATMENT: FINAL FUNCTIONAL MOBILITY ANALYSIS FROM THE PHASE 3 PEACE TRIAL (SSIEM 2024) - P3 | "The sustainability of mobility improvement long-term is highly clinically relevant in this chronic, progressive disease where a gradual decline of motor function would be expected. Palavras-chave : Pegzilarginase"

Clinical • P3 data • Movement Disorders

PEGZILARGINASE TREATMENT IN ARGINASE 1 DEFICIENCY ALLOWS FOR LIBERALISATION OF PROTEIN RESTRICTION (SSIEM 2024) - P3 | "Dietary modification may promote normal growth and minimise the burden of a restricted diet for patients and their families. Palavras-chave : arginine, diet, protein"

VALIDATION OF NOR-NOHA CONTAINING BLOOD COLLECTION TUBES FOR ACCURATE ARGININE MEASUREMENT IN PEGZILARGINASE-TREATED PATIENTS (SSIEM 2024) - "Local non-interference validation of the nor-NOHA tubes for blood collection in pegzilarginase treated patients can easily be peformed. Samples collected in nor-NOHA tubes are stable up to 14 days at room temperature."

Clinical