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

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

EXPERIENCE OF PEGZILARGINASE FOR THE TREATMENT OF ARGINASE 1 DEFICIENCY OUTSIDE CLINICAL TRIAL SETTING (SSIEM 2024) - "Data collected confirm the biochemical results demonstrated in the clinical trial setting, with further indications of opportunities for diet liberalization in ARG1-D with pegzilarginase treatment."

Clinical

AMMONIA SCAVENGER IN UREA CYCLE DISORDERS: EFFICACY OF GLYCEROL PHENYLBUTYRATE (SSIEM 2024) - "Our aim was to compare GPB with sodium phenylbutyrate (NaPB) and sodium benzoate (NaBZ)...We excluded patients treated by liver transplant or pegzilarginase... We provide evidence for a decrease of ammonia levels under GPB and observe a borderline association with reduced frequency of acute decompensations. This is consistent with previously reported data. Further studies are warranted in larger patients cohorts with isoequivalent GPB switching."

Clinical • Gastrointestinal Disorder • Hepatology • Metabolic Disorders

Meeting the Unmet Need: Introducing pegzilarginase for the treatment of Arginase 1 Deficiency (SSIEM 2024) - "After a brief introduction to the disease including prevalence, main signs and symptoms and current standard of care, a presentation on the disease pathophysiology will follow to highlight the role of arginine and its metabolites in the disease progression. Finally, the Phase III clinical trial results of pegzilarginase for the treatment of ARG1-D leading to EMA approval in December 2023 and clinical experience outside clinical trial setting will be presented."

Rare Diseases

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

New P3 trial

Lessons learned from the Arginase-1 deficiency (pegzilarginase) clinical trial (SIMD 2024) - No abstract available

Clinical

Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial. (PubMed, EClinicalMedicine) - P3 | "These results support pegzilarginase as the first potential treatment to normalize pArg in ARG1-D and achieve clinically meaningful improvements in functional mobility. Aeglea BioTherapeutics."

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

A Study of Safety of Weekly Subcutaneous Pegzilarginase in Subjects With Arginase 1 Deficiency (clinicaltrials.gov) - P3 | N=3 | Terminated | Sponsor: Aeglea Biotherapeutics | N=48 ➔ 3 | Trial completion date: May 2024 ➔ Apr 2023 | Initiation date: Jan 2023 ➔ Apr 2023 | Not yet recruiting ➔ Terminated | Trial primary completion date: May 2024 ➔ Apr 2023; Sponsor Decision

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial termination

Efficacy and Safety of Pegzilarginase in Patients With Arginase 1 Deficiency (clinicaltrials.gov) - P3 | N=32 | Completed | Sponsor: Aeglea Biotherapeutics | Active, not recruiting ➔ Completed | Trial completion date: Feb 2025 ➔ Jan 2023 | Trial primary completion date: Aug 2024 ➔ Jan 2023

Trial completion • Trial completion date • Trial primary completion date