Replagal (agalsidase alfa) / Samaritan Pharma, Takeda - LARVOL DELTA

A Study of Replagal in Children and Adults With Fabry Disease in India (clinicaltrials.gov) - P4 | N=5 | Recruiting | Sponsor: Shire | Trial completion date: Nov 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Fabry Disease • Genetic Disorders

Fabry cardiomyopathy presenting as hypertrophic phenotype with left ventricular outflow tract obstruction: a case series. (PubMed, Front Cardiovasc Med) - "Enzyme replacement therapy with agalsidase alfa in two patients was associated with stabilization or improvement in wall thickness and LVOTO. This further underscores the importance of genetic testing in the etiological diagnosis of hypertrophic cardiomyopathies. Enzyme replacement therapy may ameliorate obstruction, while mavacamten and septal reduction therapies require caution without definitive genotype-phenotype correlation."

Journal • Cardiomyopathy • Cardiovascular • Fabry Disease • Genetic Disorders • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Clinical and Biochemical Improvement After Switching From Agalsidase Alfa to Beta in a Boy With Classic Fabry Disease: A Case Report. (PubMed, Clin Case Rep) - "We described a 12-year-old boy with classic Fabry disease who was diagnosed through newborn screening. At age 10.9, after switching to agalsidase beta due to an insufficient clinical and biochemical response, his acroparesthesia resolved and plasma Lyso-Gb3 decreased. This report broadens the clinical understanding of children with Fabry disease."

Journal • Fabry Disease • Genetic Disorders

Changes in Cardiopulmonary Exercise Performance During Enzyme Replacement Therapy in Fabry Disease. (SSIEM 2026) - " A total of 35 patients completed CPET and CMR both before and during ERT; 14 received agalsidase alfa and 21 received agalsidase beta. ERT was associated with improved submaximal exercise capacity and ventilatory efficiency in Fabry disease. These CPET parameters could be sensitive markers of treatment response during ERT."

Cardiomyopathy • Cardiovascular • Fabry Disease • Genetic Disorders

Reduced cerebrovascular events after switching to agalsidase beta in Fabry disease: two case reports (SSIEM 2026) - "Despite treatment with agalsidase alfa, he experienced three recurrent strokes between 38 and 43 years of age. Although causality cannot be established, agalsidase beta may be more effective in preventing recurrent cerebrovascular events. Plasma lyso-Gb3 levels appeared to correlate with event occurrence, suggesting a potential biomarker of therapeutic response."

Case report • Clinical • Cardiovascular • Fabry Disease • Genetic Disorders • Ischemic stroke • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Long-term safety and efficacy of pegunigalsidase alfa in patients who switched from agalsidase alfa (SSIEM 2026) - No abstract available

Clinical

Positioning agalsidase alfa: personalizing therapy in Fabry disease (SSIEM 2026) - "Sponsored by Takeda"

Fabry Disease • Genetic Disorders

Twenty years of agalsidase alfa in FOS: long-term outcomes in Fabry disease (SSIEM 2026) - "Sponsored by Takeda"

Fabry Disease • Genetic Disorders

Evaluating the relationship between antidrug antibodies and efficacy and safety outcomes in patients with Fabry disease receiving enzyme replacement therapy: a systematic literature review. (PubMed, Orphanet J Rare Dis) - "This SLR found evidence that ADA positivity may be associated with increased IRR risk and may have a negative effect on some measures of ERT efficacy. Inconsistencies in the identified data were likely driven by study design differences, including prior ERT exposure, follow-up time, and ADA assessment protocols. Additional prospective studies with standardized ADA assessments and accounting for patient baseline characteristics and disease severity, are needed to better understand the clinical implications of ADA formation on ERT outcomes, including an assessment of causality."

Journal • Review • Cardiovascular • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Study of Replagal in Children and Adults With Fabry Disease in India (clinicaltrialsregister.eu) - P4 | N=5 | Sponsor: Takeda

New P4 trial • Fabry Disease • Genetic Disorders

Case Report: Is it COPD? It is Fabry disease: a case in which bronchodilators were briefly used but not continued, prioritizing enzyme replacement therapy. (PubMed, Front Pharmacol) - "During hospitalization, inhaled budesonide plus ipratropium bromide (a bronchodilator) was briefly administered...Enzyme replacement therapy (ERT) with agalsidase alfa (0.2 mg/kg every 2 weeks) was initiated as long-term disease-modifying treatment...Respiratory physicians should strictly adhere to COPD diagnostic criteria. Once Fabry disease is diagnosed, ERT should be prioritized as the disease-modifying therapy, and bronchodilators, if used at all, should be reserved for symptomatic patients as an adjunct, not a substitute."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Fabry Disease • Genetic Disorders • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Rare Diseases • Renal Disease • Respiratory Diseases

From diagnosis to disease-specific treatment: first experience with enzyme replacement therapy for Fabry disease in North Macedonia-a case series. (PubMed, Front Med (Lausanne)) - "Clinical, biochemical, cardiac, neurological, and patient-reported outcomes were prospectively evaluated after initiation of agalsidase beta (1 mg/kg) and agalsidase alfa (0.2 mg/kg), respectively. In this two-patient case series, ERT was well-tolerated and associated with substantial reduction of biochemical disease burden and stabilization of renal graft and cardiac function. However, persistent neurological impairment despite marked Lyso-Gb3 reduction suggests limited reversibility of advanced central nervous system involvement, highlighting the importance of early diagnosis, family screening, and timely initiation of disease-specific therapy in Fabry disease."

Journal • CNS Disorders • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Neuralgia • Pain • Rare Diseases • Transplantation

Pegunigalsidase Alfa in Fabry Disease Patients with Severe Infusion Reactions to Other Enzyme Replacement Therapy: A Spanish Multi-Center Experience (ERA 2026) - "This study aimed to evaluate the safety, tolerability, and clinical stability of PA in FD patients who previously discontinued agalsidase alfa or beta due to severe tolerability issues. Pegunigalsidase alfa represents a safe and effective "rescue" strategy for Fabry patients with history of severe IRRs. The PEGylation of the enzyme appears to successfully mask immunogenic epitopes, allowing for the continuation of essential therapy without compromising safety or biochemical control. These real-world data support PA as a viable alternative to overcome the limitations of other ERT in patients suffering severe infusion reactions"

Clinical • Fabry Disease • Genetic Disorders

Prevalence and sociodemographic, clinical, and genetic characteristics of Fabry disease in north-central Chile, 2013-2023. (PubMed, Mol Genet Metab Rep) - "ERT was initiated in 2016 for 58% of patients, and 55.1% received agalsidase alfa...Age at treatment initiation influences system involvement and chronic medication use. The results highlight the need for additional genetic, epidemiological, and clinical studies in the region."

Journal • Fabry Disease • Genetic Disorders • Pain • Rare Diseases

Sex-based antibody subclass maturation drives direct enzymatic inhibition in fabry disease patients receiving enzyme replacement therapy. (PubMed, Front Mol Biosci) - "Subclass-specific cross-reactivity was assessed for agalsidase alfa, agalsidase beta, and pegunigalsidase alfa. Quantitative subclass-specific ADA and complement profiling reveals sex-specific IgG4 patterns, neutralizing capacity, and ERT-specific immunogenic differences, supporting its utility for personalized therapy in Fabry disease. A novel multiplex LC-MS/MS assay quantifies ADA subclasses and complement in Fabry disease, uncovering distinct IgG4 patterns and ERT-specific profiles that enhance understanding of treatment immunogenicity."

Journal • Fabry Disease • Genetic Disorders

FABRY CARDIOMYOPATHY PRESENTING AS HYPERTROPHIC PHENOTYPE WITH LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION: A CASE SERIES (ACC 2026) - "Enzyme replacement therapy (agalsidase alfa) in two patients was associated with stabilization or improvement in wall thickness and LVOTO. Fabry cardiomyopathy can present with a hypertrophic phenotype and significant LVOTO, and is often misdiagnosed as oHCM. This further underscores the importance of genetic testing in the etiological diagnosis of hypertrophic cardiomyopathies. Enzyme replacement therapy may ameliorate obstruction, while mavacamten and septal reduction therapies require caution without definitive genotype-phenotype correlation."

Clinical • Cardiomyopathy • Cardiovascular • Fabry Disease • Genetic Disorders • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Long-Term Safety and Efficacy of Pegunigalsidase Alfa in Patients with Fabry Disease: Results from the Phase 3 BRILLIANCE Extension Study (ACMG 2026) - P3 | "At baseline, most participants had received enzyme replacement therapy (71.1% agalsidase beta; 18.6% agalsidase alfa); 25.8% had anti-drug antibodies (ADAs) against PA, and median (range) baseline estimated glomerular filtration rate (eGFR) was 77.7 (24.4, 131.0) mL/min/1.73m². These findings demonstrate that long-term treatment with pegunigalsidase alfa 1 mg/kg E2W offers a sustained safety and efficacy profile in adults with FD over a median of nearly six years, supporting its role as a viable long-term therapy."

Clinical • P3 data • Fabry Disease • Genetic Disorders

MyFABT1: Follow-up of Myocardial T1 Relaxation Time in Patients With Anderson Fabry Disease (clinicaltrials.gov) - P=N/A | N=26 | Completed | Sponsor: University Hospital, Rouen | Unknown status ➔ Completed

Trial completion • Fabry Disease • Genetic Disorders

A rapid method to reduce drug interferences for antibody measurements in pegunigalsidase alfa-treated patients with Fabry disease. (PubMed, Front Immunol) - "Alkaline pretreatment with NaOH was sufficient to eliminate up to 1 µg/ml agalsidase alfa or pegunigalsidase alfa in control sera. A second patient with pre-existing ADAs before pegunigalsidase alfa-initiation showed a massive induction of anti-PEG antibodies with inhibitory function. We present a rapid alkaline-treatment based method to overcome drug interferences to measure at least free antibodies in patients treated with pegunigalsidase alfa."

Journal • Fabry Disease • Genetic Disorders

A Study of Agalsidase Alfa Enyzme Replacement Therapy in Chinese Children and Adults With Fabry Disease (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence • Fabry Disease • Genetic Disorders

Clinical outcomes in Fabry patients switching to agalsidase beta for renal ineffectiveness of the primary Fabry therapy: a single-centre analysis. (PubMed, Clin Kidney J) - "All other parameters were stable over time. Treatment switch from agalsidase alfa or migalastat to agalsidase beta can attenuate eGFR decline and enhance lyso-Gb3 reduction, confirming the dose-dependent effect of agalsidase beta to further slow down FD progression."

Clinical data • Journal • Fabry Disease • Genetic Disorders • Renal Disease

Effect of Agalsidase Alfa on Cardiac Inflammation in Patients With Fabry Disease: A [18F]-FDG PET-CMR Study (clinicaltrials.gov) - P=N/A | N=25 | Recruiting | Sponsor: Yonsei University | Not yet recruiting ➔ Recruiting

Enrollment open • Fabry Disease • Genetic Disorders • Inflammation

Long-Term Cardiac Stability Despite Late Enzyme Replacement Therapy in Fabry Disease With Severe Renal Involvement. (PubMed, JACC Case Rep) - "Late initiation may still prevent cardiac involvement if started before myocardial damage. Delayed therapy cannot halt advanced renal deterioration. Timely diagnosis and organ screening are essential in FD."

Journal • Chronic Kidney Disease • Fabry Disease • Fibrosis • Genetic Disorders • Heart Failure • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Rare Diseases • Renal Disease • Transplantation

Effect of Agalsidase Alfa on Cardiac Inflammation in Patients With Fabry Disease: A [18F]-FDG PET-CMR Study (clinicaltrials.gov) - P=N/A | N=25 | Not yet recruiting | Sponsor: Yonsei University

New trial • Fabry Disease • Genetic Disorders • Inflammation

Assessment of α-Galactosidase A Activity Following Migalastat Therapy in Real-World Cases of Fabry Disease (KIDNEY WEEK 2025) - "Current treatment options include enzyme replacement therapy (ERT) with recombinant agalsidase alfa or beta, and pharmacological chaperone therapy with migalastat. Discussion Although migalastat is approved for Fabry disease patients with amenable mutations, its clinical efficacy appears to vary considerably depending on the specific genotype. Our findings underscore the importance of individualized assessment before initiating migalastat therapy, highlighting that treatment decisions should be based not solely on genetic amenability but also on clinical context and expected therapeutic benefit."

Clinical • Real-world • Real-world evidence • Fabry Disease • Genetic Disorders