Fabrazyme (agalsidase beta) / Sanofi - LARVOL DELTA

Progress and Challenges in the Treatment of Fabry Disease. (PubMed, BioDrugs) - "Current approved treatment includes enzyme replacement therapy (agalsidase alfa [0.2 mg/kg body weight], agalsidase beta or pegunigalsidase alfa [both 1.0 mg/kg body weight]) every other week intravenously or, if a responding ('amenable') α-galactosidase A mutation is present, oral pharmacological chaperone therapy (migalastat 123 mg, every other day). Future therapeutic options may include substrate reduction therapy, gene therapy, messenger RNA therapy, and/or vesicle-packaged enzyme replacement therapy. This review presents current and future treatment options with advantages and disadvantages of the different treatment options."

Journal • Cardiomyopathy • Cardiovascular • CNS Disorders • Fabry Disease • Gene Therapies • Genetic Disorders • Hypertrophic Cardiomyopathy • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • Renal Disease

A phase 4 study to evaluate the safety and tolerability of higher infusion rates of agalsidase beta to shorten the infusion duration in Fabry disease – Preliminary data (ERA 2025) - No abstract available

Clinical • P4 data • Fabry Disease • Genetic Disorders

THE HIDDEN CLUE: MRI PARAMETRIC MAPPING IN THE DIAGNOSIS OF FABRY DISEASE IN A FEMALE ACTIVE DUTY SOLDIER - Elizabeth R. Doman (ACC 2025) - "She was subsequently started on enzyme replacement therapy (agalsidase beta) following consultation with metabolic and heart failure specialists.Decision-making: In females, Fabry Disease may present later and more subtly due to incomplete α-galactosidase deficiency... Timely diagnosis of Fabry Disease in female patients with LVH is crucial, especially with evolving therapies. CMR parametric mapping should be a routine component in the evaluation of HCM, aiding in the differentiation of Fabry Disease from other cardiomyopathies."

Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fabry Disease • Genetic Disorders • Heart Failure • Hypertrophic Cardiomyopathy • Pulmonary Disease

Agalsidase Beta Long-Term Treatment Outcome for Fabry Disease Patients With IVS4 Mutation in Taiwan (clinicaltrials.gov) - P=N/A | N=78 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Fabry Disease • Genetic Disorders

Natural History of Renal Involvement of Fabry Disease in a Female Carrier (NKF-SCM 2025) - "She declined a renal biopsy and was treated with lisinopril. Our heterozygote carrier patient progressed to ESRD. Eight years after transplant, graft survival is excellent while getting bimonthly Fabrazyme."

Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Chronic Kidney Disease • Fabry Disease • Genetic Disorders • Hepatology • Hypertrophic Cardiomyopathy • Immunology • Inflammation • Inflammatory Arthritis • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Pain • Rare Diseases

A Multisystemic Approach to Fabry Disease in Heterozygous Females: Challenges in Recognition and Management (NKF-SCM 2025) - "She received Fabrazyme infusion every 2 weeks with symptom resolution...Due to symptom variability in heterozygous females, a high index of suspicion is critical. Early detection enables effective management and family genetic counseling."

Cardiovascular • Dyslipidemia • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Neuralgia • Pain • Rare Diseases • Renal Disease

SHORTEN: A Prospective Study to Investigate Safety and Tolerability of Shorter Infusion of Fabrazyme (clinicaltrials.gov) - P4 | N=8 | Completed | Sponsor: Sanofi | Recruiting ➔ Completed | N=18 ➔ 8 | Trial completion date: Oct 2025 ➔ Oct 2024 | Trial primary completion date: Oct 2025 ➔ Oct 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Impact of enzyme replacement therapy and migalastat on disease progression in females with fabry disease. (PubMed, Orphanet J Rare Dis) - "We conclude that treatment of females with agalsidase-beta, agalsidase-alfa, and migalastat was safe. Independent of the chosen treatment regimen, nearly all patients presented with a stable disease course over time. In our cohort, a comparison of therapy efficacies showed no relevant clinical differences between the groups."

Clinical • Journal • Fabry Disease • Genetic Disorders

A systematic literature review to evaluate the cardiac and cerebrovascular outcomes of patients with Fabry disease treated with agalsidase Beta. (PubMed, Front Cardiovasc Med) - "Rates of composite cardiac events (3.8%-24.0%; four studies, follow-up 2-10 years) and cerebrovascular events (0.0%-18.9%; 12 studies, follow-up 1-10 years) were numerically lower than rates for placebo (follow-up 3 years). Literature over the last 20 years indicates that agalsidase beta treatment may lead to stabilization or regression of cardiac structural thickness and mass, and reduction in cardiac and cerebrovascular events relative to placebo."

Journal • Review • Cardiovascular • Fabry Disease • Gene Therapies • Genetic Disorders

FABRY DISEASE NEPHROPATHY: BIOMARKERS IN PATIENTS ON ENZYME REPLACEMENT THERAPY (ISN-WCN 2025) - "Patients with Fabry nephropathy (confirmed by kidney biopsy) on ERT with agalsidase beta 1 mg/kg every other week (EOW) who normalized plasma Lyso-Gb3 levels were included...It also underscores the importance of early intervention, given that most patients in this population began treatment at a young age. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings."

Biomarker • Clinical • Cardiovascular • Fabry Disease • Gastrointestinal Disorder • Genetic Disorders • Neuralgia • Pain • Pediatrics • Renal Disease

CARAT: A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease (clinicaltrials.gov) - P3 | N=104 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Jul 2027 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ May 2026 | Recruiting ➔ Active, not recruiting

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

A real-world pharmacovigilance analysis for agalsidase beta: findings from the FDA adverse event reporting database. (PubMed, Expert Opin Drug Saf) - "The FAERS database analysis of agalsidase beta AEs identified a significant number of cardiovascular, renal, and cerebrovascular system-related reports. While agalsidase beta is generally well-tolerated, the study underscores the necessity for gender-specific treatment approaches due to the higher incidence of certain AEs in males."

Adverse events • Journal • Real-world • Real-world evidence • Cardiovascular • Fabry Disease • Genetic Disorders • Pain • Transplantation

Effects of Current Therapies on Disease Progression in Fabry Disease: A Narrative Review for Better Patient Management in Clinical Practice. (PubMed, Adv Ther) - "Four treatments are currently available for patients with FD; three enzyme replacement therapies (ERTs; agalsidase alfa, agalsidase beta, and pegunigalsidase alfa) and one pharmacological chaperone (migalastat). Real-world data raise concerns about effective in vivo amenability of some genetic variants. Future studies with direct treatment comparisons in patients with FD are needed."

Journal • Review • Cardiovascular • CNS Disorders • Fabry Disease • Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Pain • Rare Diseases • Renal Disease

Safety and Tolerability of a Shorter Agalsidase Beta Infusion Time in Patients with Classic or Later-Onset Fabry Disease. (PubMed, Biomedicines) - "Our results suggest that shortening the agalsidase beta infusion time to 90 min is safe and feasible in stably treated adult patients with Fabry disease and no recent infusion-associated reactions."

Journal • Fabry Disease • Genetic Disorders • Rare Diseases

A Phase 4 Study to Evaluate the Safety and Tolerability of Higher Infusion Rates of Agalsidase Beta to Shorten Infusion Duration in Fabry Disease: Interim Analysis (KIDNEY WEEK 2024) - P4 | "Agalsidase beta infusion was given safely at a final time of 20-minute infusion duration in ERT-experienced female and male patients without any IAR. Further findings from this study will help in establishing a protocol to reduce duration of agalsidase beta infusion and minimize the treatment burden."

Clinical • P4 data • Fabry Disease • Genetic Disorders

Comparative pharmacokinetics and pharmacodynamics of two formulations of agalsidase beta (agalsidase Biosidus) and Fabrazyme® by intravenous infusion in healthy male volunteers. (PubMed, Mol Genet Metab Rep) - "No differences were detected in adverse effects or antibody induction. This indicates that Biosidus agalsidase beta meets the criteria for being considered similar to the reference formulation Sanofi Genzyme's Fabrazyme®."

Journal • PK/PD data • Fabry Disease • Fibrosis • Genetic Disorders • Immunology • Rare Diseases

A Unique Presentation of Fabry Disease with Progressive Bilateral Hearing Loss (KIDNEY WEEK 2024) - "The patient was started on Fabrazyme infusions...It is essential to keep a high index of suspicion of unexplained nephrotic range proteinuria accompanied by paresthesia in patients. Our case demonstrated the importance of early diagnosis with kidney biopsy leading to resolution of proteinuria and symptoms after initiation of enzyme replacement.."

Fabry Disease • Fatigue • Genetic Disorders • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Otorhinolaryngology • Rare Diseases • Renal Disease

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies. (PubMed, J Inherit Metab Dis) - P3 | "BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks...Thirty patients were enrolled (24 males); 23 previously received agalsidase beta...Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease."

Journal • P3 data • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Successful rapid one-bag desensitization protocol toagalsidase-beta after a severe reaction. (PubMed, Med Clin (Barc)) - No abstract available

Journal

Comparative study on incorporation of three recombinant human α-galactosidase A drugs (agalsidases) into cultured fibroblasts and organs/tissues of Fabry mice. (PubMed, Mol Genet Metab Rep) - "But their affinity for domain 9 of cation-independent mannose 6-phosphate receptor (CI-M6PR), which exists in various cells, was higher in the order: agalsidase beta biosimilar 1 (agalsidase beta BS) > agalsidase beta > agalsidase alfa, which almost coincided with the experimental results regarding the efficiency of their incorporation into cultured fibroblasts derived from a Fabry mouse. On the other hand, no differences in the efficiency of their uptake or reduction of the accumulated substances were observed in the liver, probably due to asialoglycoprotein receptors expressed on the surface of hepatocytes. This information will be useful for making a suitable ERT plan for individual Fabry patients with various backgrounds and for developing new ERT drugs in the future."

Journal • Preclinical • Fabry Disease • Genetic Disorders • ASGR

GENETICALLY CONFIRMED FABRY DISEASE AND CLINICAL GALACTOSEMIA WITH NEGATIVE GENETIC STUDY: COINCIDENTAL FINDING OR ADD- ON EFFECT! (SSIEM 2024) - "Enzyme replacement therapy (ERT) Agalsidase beta was started soon after diagnosis for him and the other affected family members...Further studies need to be done to delineate if there is any interaction in the function between the genes for Fabry disease and galactosemia. Palavras-chave : Fabry disease, galactosemia, GALT gene, newborn screening"

Clinical • Cardiovascular • Cataract • Fabry Disease • Genetic Disorders • Metabolic Disorders • Oncology • Ophthalmology

IMPACT OF BASELINE PROTEINURIA ON RENAL OUTCOMES IN THE BALANCE STUDY OF PEGUNIGALSIDASE ALFA VS AGALSIDASE BETA IN FABRY DISEASE (SSIEM 2024) - P3 | "In BALANCE, pts randomized to PA had higher average baseline levels of proteinuria compared with the AB arm. Post hoc analyses adjusting for baseline proteinuria as a continuous variable demonstrated that the treatment difference was not statistically significant providing additional evidence of comparable effects on eGFR slope after 2 years in pts switching from AB to PA vs remaining on AB."

Fabry Disease • Genetic Disorders • Renal Disease • CST3

SWITCH FROM ENZYME REPLACEMENT THERAPY TO MIGALASTAT IN FABRY DISEASE: A REPORT OF TWO CASES (SSIEM 2024) - "Case Study/ Two sisters aged 46 and 48, diagnosed with Fabry disease (missense mutation c.326A>G) by family tree (father detected on dialysis screening), were evaluated with albuminuria and plasma Lyso-Gb3 after the switch from intravenous agalsidase beta 1 mg/kg every 2 weeks to oral migalastat 123 mg every other day. After the switch, the patients with amenable mutation to migalastat, continued at 6, 12, 24 and 36 months with normal plasma Lyso-Gb3 and albuminuria values. To date, the medical assessments have not demonstrated neurological or cardiac involvement. The switch in both cases were by patient choice, and the compliance with every other day oral administration is adequate."

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

A PHASE 4 STUDY TO EVALUATE SAFETY AND TOLERABILITY OF HIGHER INFUSION RATES OF AGALSIDASE-BETA TO SHORTEN INFUSION DURATION-INTERIM ANALYSIS (SSIEM 2024) - P4 | "Agalsidase beta infusion was given safely at a final time of 20-minute infusion duration in ERT experienced female patients without IAR. Further findings from this study will help in establishing a protocol to reduce duration of agalsidase beta infusion and minimize the treatment burden."

Clinical • P4 data • Fabry Disease • Genetic Disorders

LOWER RATE OF INFUSION-RELATED REACTIONS IN PATIENTS WITH FABRY DISEASE AFTER SWITCHING FROM AGALSIDASE BETA TO PEGUNIGALSIDASE ALFA (SSIEM 2024) - P3 | "These data suggest that some pts with a history of long-term treatment with AB and repeated IRRs may be less likely to experience IRRs or use premedication after switching to PA."

Clinical • Fabry Disease • Genetic Disorders