A Phase 2 study of migalastat hydrochloride in females with Fabry disease: Selection of population, safety and pharmacodynamic effects

Giugliani, Roberto; Waldek, Stephen; Germain, Dominique P.; Nicholls, Kathy; Bichet, Daniel G.; Simosky, Johanna K.; Bragat, Alexander; Castelli, Jeffrey P.; Elias, Benjamin; Boudes, Pol

doi:10.1016/j.ymgme.2013.01.009

Cited by 69 publications

(49 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Restoration of the mutant enzyme activity by small molecule compounds (chaperones) capable of crossing the blood-brain barrier is a new approach to treat LSDs [60], [[61]. Currently, there is an effort to identify candidate molecules [62,63].…”

Section: Potential Future Therapiesmentioning

confidence: 99%

The clinical management of type 2 Gaucher disease

Weiss

Gonzalez

Lopez

et al. 2015

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Gaucher disease, the inherited deficiency of the enzyme glucocerebrosidase, is the most common of the lysosomal storage disorders. Type 2 Gaucher disease, the most severe and progressive form, manifests either prenatally or in the first months of life, followed by death within the first years of life. The rarity of the many lysosomal storage disorders makes their diagnosis a challenge, especially in the newborn period when the focus is often on more prevalent illnesses. Thus, a heightened awareness of the presentation of these rare diseases is necessary to ensure their timely consideration. This review, designed to serve as a guide to physicians treating newborns and infants with Gaucher disease, discusses the presenting manifestations of Type 2 Gaucher disease, the diagnostic work-up, associated genotypes and suggestions for management. We also address the ethical concerns that may arise with this progressive and lethal disorder, since currently available treatments may prolong life, but do not impact the neurological manifestations of the disease.

show abstract

Section: Potential Future Therapiesmentioning

confidence: 99%

The clinical management of type 2 Gaucher disease

Weiss

Gonzalez

Lopez

et al. 2015

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

show abstract

“…The pharmacological chaperone Migalastat HCl (Galafold®, Amicus) is a newly approved oral treatment leading to enhanced plasma levels of agalsidase in disease-relevant tissues [48,49,50]. It is also expected to be beneficial in combination with classical ERT, assuring its future eligibility [48,49,50]. One limitation of chaperone therapy is the applicability to FD patients with specific GLA mutational variants, for example, N215S, P205T or R301Q [50,51].…”

Section: Emerging Therapeutic Conceptsmentioning

confidence: 99%

Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease

Oder

Nordbeck

Wanner³

2016

Nephron

View full text Add to dashboard Cite

Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

show abstract

“…Urine GL-3 levels were elevated in 7 of 9 patients at baseline and decreased between 28 and 66 % in patients with amenable mutations (n = 5) compared with an increase of between 12 and 103 % in patients with nonamenable mutations (n = 4) after treatment with migalastat hydrochloride 50, 150 or 250 mg once every other day for 48 weeks. The greatest declines in urine GL-3 occurred in patients with amenable mutations who received migalastat hydrochloride at a dose of 150 or 250 mg. Peri-tubular capillary endothelial cell GL-3 inclusions declined in four patients with amenable mutations and two with non-amenable mutations at the last available kidney biopsy [13].…”

Section: Phase IImentioning

confidence: 89%

Migalastat: First Global Approval

Markham

2016

Drugs

View full text Add to dashboard Cite

Migalastat (Galafold™)-a small molecule drug developed by Amicus Therapeutics that restores the activity of specific mutant forms of α-galactosidase-has been approved for the treatment of Fabry disease in the EU in patients with amenable mutations. Fabry disease is a rare disorder that results in a deficiency or absence of α-galactosidase, leading to accumulation of globotriaosylceramide in the lysosomes of various cells. This article summarizes the milestones in the development of migalastat leading to this first approval in the EU for the long-term treatment of adults and adolescents aged ≥16 years with a confirmed diagnosis of Fabry disease.

show abstract

A Phase 2 study of migalastat hydrochloride in females with Fabry disease: Selection of population, safety and pharmacodynamic effects

Abstract: Migalastat HCl is a candidate oral pharmacological chaperone that provides a potential novel genotype-specific treatment for FD. Treatment resulted in GL-3 substrate decrease in female patients with amenable GLA mutations. Phase 3 studies are ongoing.

Cited by 69 publications

References 15 publications

The clinical management of type 2 Gaucher disease

The clinical management of type 2 Gaucher disease

Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease

Migalastat: First Global Approval

Contact Info

Product

Resources

About