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

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

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

Matching-Adjusted Indirect Comparisons (MAICs) and Network Meta-Analyses (NMAs) of the Oral Small-Molecule Chaperone Migalastat vs. Intravenous Enzyme Replacement Therapies (ERTs) for Clinical Measures in Fabry Disease (ISPOR-EU 2025) - P1/2, P3 | "OBJECTIVES: ATTRACT (NCT01218659) compared migalastat with ERT (agalsidase alfa/beta [AGAL-α/β]) in patients with Fabry disease and amenable GLA variants. We indirectly compared migalastat with pegunigalsidase alfa (PEG) for key cardiac/renal measures and with any ERT for long-term risk of Fabry-associated clinical events (FACEs; specific cardiac/renal/cerebrovascular events/death). Systematic/targeted literature reviews identified publications/studies reporting left ventricular mass index (LVMi), annualised change in estimated glomerular filtration rate (eGFR slope) and/or FACEs... In populations matched for age, sex, eGFR/previous ERT duration and ACEi/ARB, LVMi change and eGFR slope were similar for migalastat and PEG; long-term FACE risk was similar for migalastat and AGAL-α/β."

Clinical • Fabry Disease • Genetic Disorders

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

A Novel Multiplex approach for determining anti-drug antibodies in Fabry Disease (SSIEM 2023) - "Results Pilot analysis (n=60 FD patients) using commercial ERT Agalsidase alfa as bait detected a positive response for IgG1-3 in 34-38% and IgG4 in 27% of patients...Conclusions We have developed a novel methodology for determining ADA response to ERT in FD patients. This assay can also identify differential ADA response depending on the glycosylation of the ‘bait’ used, indicating we may be able to determine difference in patient response between alternate ERTs."

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

Long-term effectiveness and safety outcomes in adults with Fabry disease treated with agalsidase alfa: 20 years of data from the Fabry Outcome Survey. (PubMed, Eur J Clin Invest) - P=N/A | "This report further supports the long-term effectiveness and safety of agalsidase alfa in adults with Fabry disease."

Journal • Cardiovascular • Fabry Disease • Genetic Disorders

Adequate hemodialysis does not compromise the cardioprotective effect of agalsidase alfa on patients with Fabry disease: a case report. (PubMed, J Med Case Rep) - "Patients with Fabry disease who are on renal replacement therapy may benefit from enzyme replacement therapy. Moreover, adequate hemodialysis does not compromise the cardioprotective effect of agalsidase-α."

Journal • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Nephrology • Rare Diseases • Transplantation

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

New trial • Real-world evidence • Fabry Disease • Genetic Disorders

A Study of Replagal in Children and Adults With Fabry Disease in India (clinicaltrials.gov) - P4 | N=5 | Recruiting | Sponsor: Shire | Active, not recruiting ➔ Recruiting

Enrollment open • Fabry Disease • Genetic Disorders

A multi-country time and motion study to describe the experience and burden associated with the treatment of Fabry disease with enzyme replacement therapy with agalsidase alfa and agalsidase beta. (PubMed, Orphanet J Rare Dis) - P | "The multi-region findings provide a more complete picture of the burden associated with ERT administration for FD treatment on patients, caregivers, and HCPs. Results may support further cost-effectiveness modelling for novel treatment approaches and inform treatment decisions and patient management."

Journal • Observational data • Fabry Disease • Genetic Disorders

Clinical Efficacy and Real-World Effectiveness of Fabry Disease Treatments: A Systematic Literature Review. (PubMed, J Clin Med) - "Enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta stabilized renal function and cardiac structure in patients with Fabry disease...Patients treated with migalastat and pegunigalsidase alfa also maintained stable renal function and cardiac structure. Overall, current treatments slow the progression of renal and cardiac decline in patients with Fabry disease. Large cohort studies with long-term follow-up and baseline stratification based on clinical phenotype are needed to address evidence gaps and provide clinicians with robust data to inform treatment decisions."

Journal • Real-world evidence • Review • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Competent expression of effective and long-acting human α-Gal A-Fc fusion protein in the milk of transgenic mice. (PubMed, Transgenic Res) - "The elimination half-life of the purified α-Gal A-Fc protein in mouse serum was 471 min, approximately 43 times longer than that of the commercially available drug Replagal. These findings facilitate the development of an efficient production system for long-acting human α-Gal A-Fc fusion protein and provide valuable insights into the utilization of transgenic large animal mammary gland bioreactors for biopharmaceuticals."

Journal • Preclinical • Fabry Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Current status of the immunogenicity of enzyme replacement therapy in fabry disease. (PubMed, Orphanet J Rare Dis) - "Currently, there are three commercially available long-term ERT treatments in patients with FD: agalsidase alfa, agalsidase beta, and more recently, pegunigalsidase alfa. Overcoming the development of ADAs is critical to improving treatment outcomes in patients with FD, different strategies have been explored to address this challenge. The present work aims to review latest developments related to all aspects mentioned above, while also analyzing the potential role of therapeutic innovations."

Journal • Review • Fabry Disease • Genetic Disorders

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

New drugs available for Fabry disease. (PubMed, Kidney Blood Press Res) - "This review focuses exclusively on newly available drugs and future therapeutic approaches for treating FD, including migalastat, pegunigalsidase alfa, substrate reduction therapy (SRT), and gene therapy. Migalastat provides benefits such as oral administration and non-immunogenicity; however, it is only appropriate for patients with "amenable" GLA variants. The recently approved pegunigalsidase alfa is a pegylated form of α-Gal A manufactured in plant cell cultures, with apparent reduced immune response and prolonged circulating half-life. SRT (venglustat, lucerastat) reduces Gb3 synthesis, helping to normalize metabolic processes while offering certain advantages such as oral administration, non-immunogenic properties, and the possible crossing of the blood-brain barrier. Clinical trials in human and animal model studies are currently investigating ex-vivo and in-vivo gene therapy techniques, showing positive early outcomes. Messages: The ongoing development..."

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

Two decades of experience of the Fabry Outcome Survey provides further confirmation of the long-term effectiveness of agalsidase alfa enzyme replacement therapy. (PubMed, Mol Genet Metab Rep) - "The mean age at which 50 % of male patients were still alive was higher in treated patients than in untreated external cohorts (75.5 vs 60.0 years). Long-term treatment with agalsidase alfa may provide renal, cardiac, and overall survival protection in FD."

Journal • Fabry Disease • Genetic Disorders

Safety analysis of self-administered enzyme replacement therapy using data from the Fabry Outcome and Gaucher Outcome Surveys. (PubMed, Orphanet J Rare Dis) - P, P=N/A | "These findings suggest that self-administration of agalsidase alfa or velaglucerase alfa infusions are not associated with additional safety risks compared with HCP-supported infusions and are a suitable option for qualifying patients. Further research is warranted to support these findings and to explore further the long-term safety and efficacy of ERT self-administration. FOS trial registration: ClinicalTrials.gov, NCT03289065. Registered 01 April 2001, https://clinicaltrials.gov/study/NCT03289065 . GOS trial registration: ClinicalTrials.gov, NCT03291223. Registered 27 July 2010, https://classic."

Journal • Cardiovascular • Fabry Disease • Gastroenterology • Gastrointestinal Disorder • Gaucher Disease • Genetic Disorders • Infectious Disease • Metabolic Disorders

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

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

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