RegulationOverseas New Drugs Urgently Needed in Clinical Settings (China), Orphan Drug (Japan), Priority Review (China), Accelerated Approval (United States)

Structure/Sequence

Sequence Code 4987

Source: *****

Clinical Trials associated with Agalsidase Beta

NCT06019728

/ CompletedPhase 4

A Study to Investigate Safety and Tolerability of Higher Infusion Rate to shORten the duraTion of FabrazymE Infusion

This Phase 4 study will evaluate the safety and tolerability of Fabrazyme at current approved dose with increases in the infusion rate and reduced infusion volume. This study aims to generate data to provide the guidance on how infusion rate can be safely increased and minimize the burden of the life-long treatment with Fabrazyme.

Start Date10 Nov 2023

Sponsor / Collaborator

Sanofi

NCT05843916

/ RecruitingPhase 3

Phase III, Open-label, Switch Over Trial of the Efficacy and Safety of Agalsidase Beta Biosidus (AGA BETA BS) in Fabry Disease Patients Previously Stabilized With Fabrazyme®

BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.

Start Date13 Dec 2022

Sponsor / Collaborator-

NCT05054387

/ CompletedPhase 4

A Phase 4, Open Label, Safety and Efficacy Study of Fabrazyme® (Agalsidase Beta) as Enzyme Replacement Therapy in Chinese Participants With Fabry Disease

This is a 54-week Phase 4, open label, single arm study to evaluate the safety and the efficacy of Fabrazyme (agalsidase beta) as enzyme replacement therapy (ERT) in Chinese participants with Fabry Disease.

Start Date13 Oct 2021

Sponsor / Collaborator

Genzyme Corp.

100 Clinical Results associated with Agalsidase Beta

100 Translational Medicine associated with Agalsidase Beta

100 Patents (Medical) associated with Agalsidase Beta

254

Literatures (Medical) associated with Agalsidase Beta

01 Mar 2025·Journal of Inherited Metabolic Disease

Correction to “Clinical Outcomes in Patients Switching From Agalsidase Beta to Migalastat: A Fabry Registry Analysis”

01 Feb 2025·Advances in Therapy

Effects of Current Therapies on Disease Progression in Fabry Disease: A Narrative Review for Better Patient Management in Clinical Practice

Review

Author: Pieruzzi, Federico ; Cianci, Vittoria ; Tuttolomondo, Antonino ; Pisani, Antonio ; Biagini, Elena ; Mignani, Renzo ; Pieroni, Maurizio

Fabry disease (FD) is a rare lysosomal storage disorder that is characterized by renal, neurological, and cardiovascular dysfunction. 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). This review focuses on the evidence for the benefits of ERTs and migalastat, and provides an overview of their impact on disease manifestations and quality of life (QoL). Agalsidase beta is associated with renal, neurological, and cardiovascular benefits, and may prevent renal disease progression. Agalsidase alfa provides stabilizing effects across all main organ systems, although minor sex-specific differences exist in patients with more advanced baseline disease. The benefits of agalsidase alfa and agalsidase beta are similar but depend on the extent of baseline disease. Some data indicate that agalsidase beta may be preferable over the longer term. Both agalsidase alfa and agalsidase beta are associated with improved gastrointestinal and pain symptoms, as well as improved QoL. Patients with advanced end-organ damage tend not to respond as optimally to ERTs as those who initiate ERTs before irreversible organ fibrosis develops, highlighting the need for early treatment initiation. Migalastat, which is only approved for patients with amenable missense gene variants, generally stabilizes renal parameters and provides cardiovascular benefits. Migalastat also improves diarrhea and pain, and stabilizes QoL (although ERT may be more effective for pain management), but the neurological effects of migalastat have not been studied. 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.

01 Jan 2025·Journal of Inherited Metabolic 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

Article

Author: Longo, Nicola ; Chertkoff, Raul ; Wilcox, William R. ; Waldek, Stephen ; Hughes, Derralynn ; Eyskens, François ; Goker‐Alpan, Ozlem ; Pisani, Antonio ; Alon, Sari ; Sakov, Anat ; Holida, Myrl ; Bernat, John A. ; Rocco, Rossana ; Deegan, Patrick ; Feldt‐Rasmussen, Ulla ; Wallace, Eric ; Almon, Einat Brill ; Tøndel, Camilla ; Warnock, David G. ; Linhart, Aleš

AbstractPegunigalsidase alfa, a PEGylated α‐galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half‐life than other ERTs administered intravenously every 2 weeks (E2W). 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. Primary objective assessed safety, including number of treatment‐emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4‐week dosing interval. Thirty‐three of 182 TEAEs (in 9 patients) were considered treatment‐related; all were mild/moderate. No patients developed de novo anti‐drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter‐quartile range) eGFR change from baseline over 52 weeks was −1.9 (−5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: –2.4 [−5.2; 3.2]; females [n = 6]: −0.7 [−9.2; 2.0]). Overall, median eGFR slope was –1.9 (−8.3; 1.9) mL/min/1.73 m2/year (ADA‐negative [n = 20]: −1.2 [−6.4; 2.6]; ADA‐positive [n = 9]: −8.4 [−11.6; –1.0]). Lyso‐Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA‐positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W.Take‐home messageTreatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

News (Medical) associated with Agalsidase Beta

13 Mar 2025

·fabrydiseasenews.com

Fabry may be underdiagnosed contributor to heart disease: Case

The case of a South African man diagnosed with hypertrophic cardiomyopathy (HCM), a disease of the heart muscle, who was later found to also have Fabry disease, suggests the rare inherited condition may be an underdiagnosed contributor to HCM, per a report.The researchers say this case “demonstrates the importance of screening for [genetic] variants in patients with apparent HCM.”The man’s Fabry disease was found nine years after his HCM diagnosis, when genetic testing — not widely available in the region the patient lived — was ultimately done, highlighting “the role of research and humanitarian programs in clinical practice in resource-limited settings,” the team wrote.Reviewing his medical history, doctors found that the man had been experiencing other signs of Fabry disease for decades, but it wasn’t until the genetic testing was performed that he was able to get the right diagnosis and treatment.“These findings indicate that FD [Fabry disease] may represent an important, but underdiagnosed, contributor to HCM in South Africa,” the researchers wrote.The case report, “Identification of an Ultra-Rare GLA Frameshift Variant in a South African Family With Hypertrophic Cardiomyopathy: A Case Report,” was published in the journal Cureus.In Fabry disease, mutations in the GLA gene lead to a lack of functional alpha-galactosidase A (alpha-Gal A) enzyme. Consequently, a fatty substance that alpha-Gal A normally breaks down, called globotriaosylceramide or Gb3, toxically accumulates throughout the body, leading to a wide range of symptoms.Cardiac issues are common in Fabry patients and may include left ventricular hypertrophy (LVH), in which the heart’s left ventricle — which normally pumps blood out to the body — becomes thick and enlarged, and the heart has a harder time pumping blood.When LVH is seen as the main feature of Fabry, without obvious involvement of other organs, it may be mistaken for the more common HCM. While it also involves a thickening of the left ventricle, HCM occurring on its own is a distinct cardiac condition.Fabry patients may receive cardiac medications such as those used to treat HCM, but the cornerstone of disease care is enzyme replacement therapy, or ERT. As its name suggests, ERT supplies the body with a version of the missing alpha-Gal A enzyme. It thus is critical to accurately distinguish between isolated HCM and Fabry with cardiac manifestations.In this case, the patient had been diagnosed with HCM at age 53, when he experienced atrial fibrillation, or an irregular and rapid heartbeat, and a stroke, in which blood flow to the brain is disrupted. His mother also had been diagnosed with HCM.A further review of the patient’s medical history showed that the man had experienced symptoms consistent with Fabry disease for decades.In his mid 20’s, he was treated for recurrent collapsed lungs. Then, in his late 40’s, he experienced a transient ischemic attack (TIA), sometimes known as a mini-stroke. Both lung disease and TIAs are known features of Fabry disease.After being diagnosed with HCM, the patient continued to experience a number of health issues, including progressive cardiac problems, worsening shortness of breath, and signs of chronic kidney disease. He also had another TIA, as well as symptoms of nerve damage with erectile dysfunction, intermittent pain, and worsening anxiety.Nine years after the HCM diagnosis, the man developed signs of heart failure. This prompted clinicians to perform genetic testing, which revealed a very rare mutation in the GLA gene (c.774_775delAC) that was also found in the patient’s mother. A blood test showing that alpha-Gal A enzyme activity was reduced confirmed the Fabry diagnosis.The patient was started on ERT. The researchers indicated that they don’t expect the treatment to reverse the existing heart disease, because such treatments have a limited ability to clear Gb3 from heart cells.Rather, “the aim of treatment is to preserve the function of organs more responsive to ERT such as the kidneys and lungs,” the researchers wrote.After a year, the man’s kidney, lung, and heart function have remained stable, and he has reported that his anxiety and fatigue are reduced.“This case demonstrates the importance of exploring the medical history of patients presenting with HCM in more detail, as noncardiac disease may precede cardiac presentation,” the researchers wrote, noting that testing for GLA mutations may also be warranted when unexplained LVH is present.The study also highlights the challenges of diagnosing and treating rare diseases like Fabry in resource-limited areas.Genetic testing was not readily available where the man lived, and as such, his testing had been performed as part of a genetic research project. Likewise, due to its cost, ERT is not easily accessible. This man became the first adult to receive Fabry ERT in the state sector of South Africa through a humanitarian program sponsored by Sanofi, which markets the ERT Fabrazyme (agalsidase beta), according to the researchers.Overall, the team noted, Fabry “is likely to be underreported in South Africa, with patients receiving inappropriate treatment, if any, for their condition.”Cases such as this one “[emphasize] the need for genetic testing to become routine in all healthcare settings, where identification of rare genetic diseases can have profound impacts on patient management and family screening programs,” the researchers wrote.

23 Jan 2025

·fabrydiseasenews.com

ERT treatment guidelines lead to stable Fabry in women: Study

Women severely affected by Fabry disease and treated with enzyme replacement therapy (ERT) and untreated women with less severe symptoms showed broadly stable disease course over five years, a study in Germany found.Treatment decisions were primarily based on the European guidelines for females with Fabry, which recommend initiating treatment at the first manifestation of Fabry-related organ involvement or pain. The guidelines “appear to have been correct” for most of the women in the study, the researchers wrote. Still, “it is crucial to explore if organ involvement is [Fabry]-related in order to make the correct treatment decision,” they wrote.The study, “Impact of enzyme replacement therapy on clinical manifestations in females with Fabry disease,“ which was published in the Orphanet Journal of Rare Diseases.According to current European guidelines, ERT for female Fabry patients should start after the first manifestation involving the kidneys, heart, or nervous system, or if pain or severe gastrointestinal complaints are present.A previous study from the research team suggested that treatment for women with Fabry in that country generally aligns with the current European Fabry guidelines. Still, one-third of patients were left untreated despite organ involvement.In Fabry, mutations in the GLA gene disrupt the production and/or function of the enzyme alpha-galactosidase A (alpha-Gal A). A lack of this enzyme’s activity leads to the toxic build-up of fatty substances called globotriaosylceramide (Gb3) and lyso-Gb3 in the body’s cells, particularly in the heart, kidneys, and nervous system.Because the GLA gene is located on the X chromosome, males with one copy of the gene tend to have more severe symptoms that develop earlier than females with two copies. For females, even if one copy of the GLA gene is mutated, the second copy is typically normal, so disease onset, progression, and severity varies more than in males.The researchers said this discrepancy means more data are required for female patients to analyze the effect of ERT or to exclude potential disease progression in untreated females. They retrospectively analyzed data from 159 women with Fabry collected at three visits at six Fabry centers in Germany. All participants were either untreated with ERT or on a stable dose of agalsidase alfa, sold as Replagal outside the U.S., or agalsidase-beta, sold as Fabrazyme, for at least six months.Seventy-one patients were untreated, 47 were newly treated, and 41 had received long-term ERT. The untreated group was significantly younger, had the lowest blood levels of lyso-Gb3, and had the least frequent Fabry-related symptoms and manifestations, including edema (swelling), pain, fatigue, and heart involvement.The newly ERT-treated group had the highest blood pressure values and showed more frequent albuminuria, a sign of kidney disease. Median eGFR values, a test for kidney function, and the number of ischemic attacks/strokes were similar before the first visit across all three groups.Fabry-related pain was the most frequent initial manifestation in all three groups, followed by heart and kidney involvement. Gastrointestinal symptoms were reported by 37.3% of untreated patients.About 90% of patients who received ERT showed at least one organ manifestation, with most having two or more, “justifying treatment according to current European guidelines,” the team noted. In contrast, one in four untreated patients showed no organ damage or manifestations at the first visit, and one-third had more than one manifestation.Between the first and third visits, transient ischemic attacks/strokes occurred more often among newly ERT-treated patients than in untreated and long-term ERT patients. Four of the five newly treated patients who experienced these events had no history of such complications.At the same time, heart involvement remained stable across all three groups. No pacemakers for irregular heartbeats were needed among untreated patients, while nearly one in ten (8.5%) newly treated patients and one in 20 (4.5%) long-term ERT patients required pacemakers.Mean eGFRs for kidney function in newly treated and long-term ERT-treated patients slightly decreased over time, but remained stable within the untreated group. The albumin-to-creatinine ratio from urine, another kidney function test, was stable in all three groups over time.Disease severity slightly increased over time in all groups, as indicated by the Disease Severity Scoring System (DS3) and the Mainz Severity Score Index (MSSI). Blood tests showed lyso-Gb3 values in the newly ERT-treated group dropped significantly over time while remaining stable in the other two groups.“Both severely affected females who were treated and less severely affected untreated females showed a broadly stable disease course over 5 years,” the researchers wrote. “The treatment decisions based on the European guidelines appear to have been correct in most patients of our cohort.”

Clinical ResultAHA

18 Nov 2024

·endpts.com

FDA offers more guidance on developing cell and gene therapies

The FDA on Monday offered new draft guidance to help drugmakers understand the nuts and bolts of FDA processes for developing and submitting an application for a new cell or gene therapy, from pre-IND meetings to long-term safety monitoring. The 40-page draft question-and-answer document was created as part of FDA’s commitment under the latest user fee deal, and as part of the agency’s wider work to increase the efficiency of cell and gene therapy development. “This guidance is intended to support the development of CGT products by providing a repository of common questions posed to the Office of Therapeutic Products (OTP),” the agency said in the draft. Building on other, more specific guidance the agency has released around cell and gene therapy development, the draft begins with a focus on what’s important to include in quality IND submissions. It also touches on when FDA recommends a pre-BLA meeting, and what should be included in a request for one. As far as how much and what type of proof-of-concept data are appropriate prior to conducting a clinical trial, the agency emphasizes that, “The adequacy of the nonclinical data to support administration of the investigational CGT product in the proposed clinical trial is determined based on the review of the [proof-of-concept] and safety data in the IND.” The guidance spells out when a surrogate endpoint can be used to support a potential accelerated approval, and several factors to be considered when assessing whether a biomarker may work as a surrogate endpoint. The use of biomarkers as surrogates has been ongoing for at least two decades, when Sanofi’s Fabrazyme initially won accelerated approval in 2003 thanks to a biomarker serving as a surrogate endpoint. Building off chemistry, manufacturing and control (CMC) guidance for gene therapies from 2020, the Q&A also discusses CMC issues sponsors should consider as they prepare to submit a BLA, such as how nonclinical and CMC safety testing data “must be provided prior to initiation of Phase 1 studies, along with basic product and process characterization data.” The guidance also explains short- and long-term safety monitoring in trials of investigational cell and gene therapies, explaining how FDA advises sponsors to observe subjects for delayed adverse events “for as long as 15 years following exposure” to an investigational product.

Gene TherapyAccelerated Approval

100 Deals associated with Agalsidase Beta

External Link

KEGG	Wiki	ATC	Drug Bank
D03228	Agalsidase Beta	A16AB04	DB00103

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Fabry Disease	Iceland	Sanofi	03 Aug 2001
Fabry Disease	European Union	Sanofi	03 Aug 2001
Fabry Disease	Liechtenstein	Sanofi	03 Aug 2001
Fabry Disease	Norway	Sanofi	03 Aug 2001

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 2	United States	Genzyme Corp.	01 Dec 2002
Fabry Disease	Phase 1	Puerto Rico	Genzyme Corp.	01 Oct 1999

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00233870 (Pubmed \| Orphanet J Rare Dis)	Not Applicable	Fabry Disease	-	Agalsidase beta	(pdnxgnhaic) = qxqzzjapkj hvebhukbjc (llzpevqtpy ) View more	-	24 Jul 2023
Pubmed Manual	Phase 2	Fabry Disease	10	Agalsidase Beta	jbuosfdbgl(lqeynctbku) = decreased 4.01 ± 1.29 μg/mL jesaaxeprv (hsoxxjuweu ) View more	Positive	16 Sep 2022
NCT00701415 (FIELD, CTgov)	Phase 3	Fabry Disease	31	Agalsidase beta (Fabrazyme 0.5 mg/kg)	fwwsjkzxwy(mtzgkvdihw) = btddkkgywj wgrngxnuhi (bmweifeotu, ogcyjshnhn - ntdbbnzwfw) View more	-	29 Jun 2016
NCT00701415 (FIELD, CTgov)	Phase 3	Fabry Disease	31	Agalsidase beta (Fabrazyme 1.0 mg/kg)	fwwsjkzxwy(mtzgkvdihw) = kzkqrendbd wgrngxnuhi (bmweifeotu, qjgxuxfvol - vfdprfigca) View more	-	29 Jun 2016
NCT00074971 \| NCT00196742 (Pubmed \| Hum Genet \| J Med Genet) Manual	Phase 3	Fabry Disease	52	agalsidase beta	(qnqqfpywil) = bmbzipvnir jjktaxieph (wobynszhhz ) View more	Positive	01 May 2015
NCT00140621 (CTgov)	Phase 4	Fabry Disease	6	Agalsidase beta	tajdrufvaj(krlsgycgrs) = tmhtuksnfj hwsszoqsaj (ksyhshtjjd, zrfpfblowj - wcwplhtauu) View more	-	15 Apr 2015
NCT01650779 (CTgov)	Phase 4	Fabry Disease	15	Agalsidase beta	guttdsmdax(uptniglogz) = hfkpxrqoso vkahbitadz (mqbegalkoi, dcdxqfeoee - rhecatoxmq) View more	-	10 Jul 2014
ERA2012	Not Applicable	Fabry Disease	10	Agalsidase-alfa	gsmiaqovro(zjyhfxevhy) = dkexznsswa xgtwjgagzw (loincrbios ) View more	Positive	01 May 2012
ERA2012	Not Applicable	Fabry Disease	10	Agalsidase-beta	gsmiaqovro(zjyhfxevhy) = iblnekkzrg xgtwjgagzw (loincrbios ) View more	Positive	01 May 2012
NCT00081497 (CTgov)	Phase 4	Fabry Disease	67	agalsidase beta	xgucxxmcih(frtcxcpjcd) = lxzgnpvgec hszexhomjm (mxeazmbpiv, bsulgggust - nokflxkqct) View more	-	18 Aug 2010
NCT00074958 (CTgov)	Phase 2	Fabry Disease	16	Fabrazyme (agalsidase beta)	xpiinevfpl(ylgzuctpaq) = lqhnsfmqir heovgwahmh (uburcdgsxg, xondvnhiix - lwonazqden) View more	-	16 Jun 2009
NCT00196716 (CTgov)	Phase 2	Fabry Disease	21	Fabrazyme (agalsidase beta)	tgfhexznhi(fbkpgpprdj) = okumunzwni ktplntdfdg (udsawsjgcp, sedcddmmio - xrqpdfjdxk) View more	-	02 Apr 2009

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