Once every 4 weeks - 2 mg/kg of pegunigalsidase alfa for treating Fabry disease Preliminary results of a phase 3 study

Holida, Myrl; Bernat, John A.; Longo, Nicola; Göker-Alpan, Özlem; Wallace, Eric; Schiffmann, Raphael; Deegan, Patrick; Khan, Nabeel; Tøndel, Camilla; Eyskens, François; Hughes, Derralynn; West, Michael; Giraldo, Pilar; Ezgu, Fatih Süheyl; Almon, Einat; Alon, Sari; Amit-Cohen, Bat-Chen; Szlaifer, Mali; Chertkoff, Raul; Wilcox, William R.

doi:10.1016/j.ymgme.2018.12.176

Cited by 7 publications

(5 citation statements)

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“…Pegunigalsidase alfa Higher plasma half-life [100][101][102], allowing a monthly infusion [102] Anti-drug antibodies in 19% of cases [101] Plant-derived protein with a different glycosylation pattern-possible immunogenicity issues? [100] Unclear effect on the immune system [13] No crossing of the blood-brain barrier [13] Lifelong therapy requiring intravenous administration [13] Moss-derived α-galactosidase A Higher cellular uptake via the mannose receptors [104,105] Plant-derived protein with a different glycosylation pattern-possible immunogenicity issues?…”

Section: Potential Advantages Potential Limitationsmentioning

confidence: 99%

“…Pegunigalsidase alfa, a chemically modified α-galactosidase A enzyme produced in a tobacco plant cell based ProCellEX system, is constituted by two subunits of α-galactosidase A covalently bound by a chain of polyethylene glycol (PEG), which increases its stability and reduces its clearance, thereby extending its plasma half-life [ 100 , 101 , 102 ] and allowing a monthly infusion [ 102 ]. Being plant-derived, this enzyme does not display M6P on their surface glycans [ 100 ], which suggests an alternative mechanism of cell uptake and may result in a different biodistribution profile from agalsidase alfa and agalsidase beta.…”

Section: Migalastatmentioning

confidence: 99%

“…This enzyme has already been demonstrated (i) to decrease plasma lyso-Gb3 levels and peritubular capillary Gb3 deposits in the kidney; (ii) to improve the BPI score, gastrointestinal symptoms, and MSSI; (iii) and to maintain eGFR, proteinuria and LV mass on MRI with no “de novo” cardiac fibrosis [ 101 ]. Studies to further test its efficacy are ongoing [ 102 , 103 ]. Anti-drug antibodies occurred in 19% of cases and became negative after 1 year, suggesting induction of immune tolerance [ 101 ], but its effect on the immune system is not yet completely clear [ 13 ].…”

Section: Migalastatmentioning

confidence: 99%

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Fabry Disease Therapy: State-of-the-Art and Current Challenges

Azevedo

Gago

Miltenberger-Miltényi

et al. 2020

IJMS

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Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that “in vitro” amenability may not always reflect “in vivo” amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD.

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Section: Potential Advantages Potential Limitationsmentioning

confidence: 99%

Section: Migalastatmentioning

confidence: 99%

Section: Migalastatmentioning

confidence: 99%

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Fabry Disease Therapy: State-of-the-Art and Current Challenges

Azevedo

Gago

Miltenberger-Miltényi

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…[ 58 ] Second, the feasibility of monthly 2 mg/kg PegA infusion was evaluated in the BRIGHT (NCT03180840) study. [ 59 ] This regimen was well-tolerated in FD patients previously treated with standard ERT. Finally, the safety and effectiveness of switching from agalsidase-α to 1 mg/kg biweekly PegA infusions were tested in the BRIDGE (NCT03018730) study.…”

Section: Treatmentmentioning

confidence: 99%

“…55 This potentially ground-breaking preclinical research was followed by three randomised clinical trials (RCTs). [58][59][60] First, patients with worsening renal failure despite long-term ERT with agalsidase-β were enrolled in the BALANCE (NCT02795676) trial for the first head-tohead comparison between first-and second-generation ERT. 58 Second, the feasibility of monthly 2 mg/kg PegA infusion was evaluated in the BRIGHT (NCT03180840) study.…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

Cardiovascular Involvement in Fabry’s Disease: New Advances in Diagnostic Strategies, Outcome Prediction and Management

et al. 2023

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Cardiovascular involvement is common in Fabry’s disease and is the leading cause of morbidity and mortality. The research is focused on identifying diagnostic clues suggestive of cardiovascular involvement in the preclinical stage of the disease through clinical and imaging markers. Different pathophysiologically driven therapies are currently or will soon be available for the treatment of Fabry’s disease, with the most significant benefit observed in the early stages of the disease. Thus, early diagnosis and risk stratification for adverse outcomes are crucial to determine when to start an aetiological treatment. This review describes the cardiovascular involvement in Fabry’s disease, focusing on the advances in diagnostic strategies, outcome prediction and disease management.

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Fabry disease: a rare disorder calling for personalized medicine

Lerario,

Monti,

Ambrosetti

et al. 2024

Int Urol Nephrol

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Fabry Disease (FD) is a genetic disease caused by a deficiency in the activity of lysosomal galactosidase A (α-GalA), an enzyme responsible for the catabolism of globotriaosylceramide (Gb3). Since lysosomes are present throughout the body and play a crucial role in catabolism and recycling of cytosolic compounds, FD can affect multiple organs and result in various symptoms, including renal, cardiovascular, neurological, cutaneous, and ophthalmic manifestations. Due to the nonspecific symptoms and the rarity of FD, it is often diagnosed late in life. However, introducing targeted therapies such as enzyme replacement therapy (ERT) and chaperone therapy has significantly improved FD's natural history and prognosis by restoring α-GalA enzyme activity. Despite the advancements, there are limitations to the currently available therapies, which has prompted research into new potential treatments for FD, including alternative forms of enzyme replacement therapy, substrate reduction therapy, mRNA therapy, and genetic therapy. In this review, we analyze the epidemiology, pathophysiology, and treatment of FD, with particular emphasis on promising therapeutic opportunities that could shift the treatment of this rare disease from a standardized to a personalized approach soon.

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Once every 4 weeks - 2 mg/kg of pegunigalsidase alfa for treating Fabry disease Preliminary results of a phase 3 study

Cited by 7 publications

References 0 publications

Fabry Disease Therapy: State-of-the-Art and Current Challenges

Fabry Disease Therapy: State-of-the-Art and Current Challenges

Cardiovascular Involvement in Fabry’s Disease: New Advances in Diagnostic Strategies, Outcome Prediction and Management

Fabry disease: a rare disorder calling for personalized medicine

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