Fabrazyme (agalsidase beta) / Sanofi - LARVOL DELTA

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

10-Year Clinical Course of a Patient with Fabry Cardiomyopathy and Severe Left Ventricular Hypertrophy (SSIEM 2026) - "ERT with agalsidase-beta was initiated... This case demonstrates a clinically important dissociation between reduction in LV hypertrophy and progressive deterioration of LV function in advanced Fabry cardiomyopathy under long-term ERT. These findings suggest that reduction in LV mass does not necessarily reflect disease modification once myocardial fibrosis is established. Our observation highlights a critical therapeutic window in Fabry disease and underscores the limited reversibility of advanced-stage cardiomyopathy, emphasizing the need for earlier diagnosis and intervention."

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fabry Disease • Fibrosis • Genetic Disorders • Heart Failure • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Rare Diseases

Responsiveness of Early Signs and Symptoms of Fabry Disease in Agalsidase Beta-Treated US Pediatric Patients (SSIEM 2026) - P | "Peripheral pain and heat/cold intolerance were the most prevalent baseline symptoms in pediatric patients with Fabry disease in the US. Agalsidase beta therapy was associated with sustained normalization of biomarker levels. Renal, cardiac and cerebrovascular events were rare during agalsidase-beta therapy in pediatric patients; further follow-up is needed to define long-term outcomes in this population."

Clinical • Cardiovascular • Fabry Disease • Genetic Disorders • Pediatrics • Ventricular Tachycardia

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

Enhancing Enzyme Replacement Therapy in Lysosomal Storage Disorders: Faster Infusion Rates Across the UK (SSIEM 2026) - "Frequently accelerated treatments included agalsidase beta, alglucosidase alfa, avalglucosidase alfa, cipaglucosidase alfa with miglustat, laronidase, elosulfase, idursulfase, and galsulfase. Accelerated ERT infusion rates outside SmPC recommendations are already in widespread use across UK LSD centres without evidence of elevated infusion-related adverse events. While practice varies, centres successfully shorten treatment duration by modifying infusion protocols. Wider sharing of local protocols and outcomes may improve equity for patients across centres, reduce treatment burden and shorter nursing homecare visits which in turn will reduce financial burden to the NHS."

Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

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

Clinical outcomes of agalsidase Beta (fabrazyme) in Chinese fabry disease patients with proteinuria: a case series. (PubMed, Front Pediatr) - "The management of proteinuria required concomitant RAAS inhibition. Family cascade screening remains critical for early diagnosis."

Clinical data • Journal • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Fabry Disease • Gastrointestinal Disorder • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Neuralgia • Pain • Rare Diseases • Renal Disease • Transplantation

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

Integrated Glyco-Analytical Strategy for Comprehensive Characterization of a Complex Therapeutic Glycoprotein: Fabrazyme. (PubMed, Int J Mol Sci) - "Desialylation reduced spectral complexity, thereby facilitating accurate mass matching with a combinatorial library generated from glycopeptide-level data. The complementary use of these three analytical levels provides a comprehensive view of Fabrazyme glycosylation, offering a robust reference for quality control and biosimilar development."

Journal

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

Successful utilization of immune tolerance induction in a pediatric patient with classic Fabry disease: a case report (ACMG 2026) - "This case report details the treatment course of a pediatric patient with classic Fabry disease who received ITI with rituximab, methotrexate, and IVIG concomitant with ERT. Tolerance to ERT can reduce the risk of antibody development to therapy, decreasing the risk of infusion related reactions and improving the long-term efficacy of this lifelong therapy. Conclusion This case report highlights the identification of a high-risk phenotype requiring initiation of enzyme replacement therapy with agalsidase beta and implementation of immune tolerance management to improve patient outcomes in a pediatric male patient with classical Fabry disease."

Case report • Clinical • Fabry Disease • Genetic Disorders • Ophthalmology • Pediatrics • Pompe Disease

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

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

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

Historical Control Analysis Demonstrates Greater Long-Term Reduction in Plasma Globotriaosylceramide (Gb3) by Venglustat Compared With Placebo or Agalsidase Beta in Male Patients With Classic Fabry Disease. (PubMed, Mol Genet Genomic Med) - "Venglustat showed significantly greater reductions in plasma GL-3 concentrations than placebo after 6 months and agalsidase beta after 24 and 36 months. These findings support the potential of long-term venglustat treatment to reduce GL-3 accumulation in patients with classic FD. Further studies are needed to confirm clinical benefit."

Biomarker • Clinical • Journal • Fabry Disease • Genetic Disorders

A Rare Case of Coexisting Fabry Disease and IgAN Progressing to ESRD (KIDNEY WEEK 2025) - "Post-transplant, she remained stable on a regimen of prednisone, tacrolimus, and mycophenolate, with continued Agalsidase beta. While IgAN is typically immune-mediated, it is unclear if FD can trigger autoantibodies production, indicating potential shared immunologic link. Early recognition, multidisciplinary approach and tailored therapy, including enzyme replacement therapy and renal transplantation, are crucial for optimizing outcomes in these rare and complex nephropathies."

Clinical • Chronic Kidney Disease • Cognitive Disorders • Fabry Disease • Genetic Disorders • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Neuralgia • Rare Diseases • Renal Disease

Silent Symptoms, Serious Findings: Fabry Disease in a Heterozygous Woman (KIDNEY WEEK 2025) - "In addition to an ACE inhibitor, agalsidase beta was initiated to slow the progression of kidney disease...In our patient, the Y207X mutation led to premature termination of GLA protein expression, resulting in a nonfunctional protein. Genetic results alone do not predict severity; thus, close monitoring and early treatment are essential to prevent complications."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiomyopathy • Cardiovascular • CNS Disorders • Fabry Disease • Genetic Disorders • Hypertension • Hypertrophic Cardiomyopathy • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Obesity • Otorhinolaryngology • Psychiatry • Rare Diseases • Renal Disease

Cost-Utility Analysis of Pegunigalsidase Alfa Compared to Agalsidase Alfa and Agalsidase Beta for the Treatment of Adult Patients With Fabry Disease in Greece (ISPOR-EU 2025) - "Enzyme replacement therapies (ERT) (agalsidase-alfa, agalsidase-beta, pegunigalsidase-alfa), along with migalastat have shown clinical benefits; however, their economic value remains a key consideration for payers. Treatment with pegunigalsidase-alfa results in less costs and potentially improves health outcomes compared to currently used ERTs for adult patients with FD in Greece."

Clinical • HEOR • Fabry Disease • Genetic Disorders • Rare Diseases

Pegunigalsidase Alfa Elfabrio® as a Long-Term Enzyme Replacement Therapy in Adults With Fabry Disease: A Systematic Literature Review (ISPOR-EU 2025) - P1/2, P3 | "Pegunigalsidase alfa demonstrated improved efficacy and a comparable safety profile to agalsidase beta, supporting its long-term use in adults with Fabry disease but further research is warranted to assess its comparative effectiveness versus agalsidase alfa."

Clinical • Review • Fabry Disease • Genetic Disorders

What Has Worked Well in Fabry Disease? An HTA Landscape Assessment Study (ISPOR-EU 2025) - "These submissions were assessed for the final recommendations for reimbursement and key issues. We found four treatments for FD, including agalsidase alfa, agalsidase beta, pegunigalsidase alfa, and migalastat. This analysis suggests that HTA journey of treatments in FD has been challenging and inconsistent, with most HTA receiving conditional recommendations. While orphan medications address medical needs for a small number of patients and their development should be encouraged, HTA agencies mainly assess it from economic value in addition to the clinical benefits over the existing standard care."

Fabry Disease • Genetic Disorders • Rare Diseases

Pooled analysis of the effect of pegunigalsidase alfa on renal function: Data from 113 patients in the pegunigalsidase alfa clinical trial program (SSIEM 2023) - "The safety and efficacy of PA has been investigated in 4 clinical trials and 3 long-term extensions, consisting of ERT-naïve patients (pts) and those who switched from agalsidase beta (AB) or alfa (AA). In this pooled analysis that included a large proportion of pts with prior ERT exposure, PA- treated pts showed slower decline in eGFR over time, indicating that PA can be a valuable option for FD, regardless of gender or prior ERT exposure."

Retrospective data • Fabry Disease • Genetic Disorders

LYSO-GB3 Normalisation in Fabry Disease-Treated Patients (SSIEM 2023) - "Eight Fabry disease patients with a confirmed diagnosis and normalised plasma Lyso-Gb3 with agalsidase beta (1 mg/kg each other week) were included. The mean patient age ("

Clinical • Cardiovascular • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Renal Disease

Safety and tolerability of pegunigalsidase alfa: Insights from a single site experience from the Expanded Access Program in the United States (SSIEM 2023) - P | "The enrollment reasons included poor tolerability of agalsidase beta (AB), disease progression on AB, and worsening of proteinuria on migalastat...One ERT-naïve male with classic FD enrolled due to poor tolerability with venglustat and withdrew after experiencing a serious adverse event (SAE) of hypersensitivity reaction with the third PA infusion (antidrug antibody [ADA]-negative at baseline [BL])... PA is a novel ERT that is well tolerated in patients with FD. While healthcare providers should remain vigilant for possible hypersensitivity reactions, PA may offer the benefit of reduced infusion duration and lower premedication burden for some patients with poor tolerability with other ERTs."

Clinical • Cardiovascular • Fabry Disease • Genetic Disorders • Immunology • Movement Disorders • Renal Disease • Ventricular Tachycardia

Managing Severe Infusion Reactions to Fabrazyme in Child with Fabry Disease (ACAAI 2025) - "For children in whom ERT is essential and no alternative therapies exist, a modified protocol offers a safe approach to reinitiating treatment. Individualized strategies are critical to ensure adequate treatment for these patients."

Clinical • Fabry Disease • Genetic Disorders • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases