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Treatment of Fabry's Disease With Migalastat: Outcome From a Prospective Observational Multicenter Study (FAMOUS)
Author(s) -
Lenders Malte,
Nordbeck Peter,
Kurschat Christine,
Karabul Nesrin,
Kaufeld Jessica,
Hennermann Julia B.,
Patten Monica,
Cybulla Markus,
Müntze Jonas,
Üçeyler Nurcan,
Liu Dan,
Das Anibh M.,
Sommer Claudia,
Pogoda Christian,
Reiermann Stefanie,
Duning Thomas,
Gaedeke Jens,
Stumpfe Katharina,
Blaschke Daniela,
Brand StefanMartin,
Mann W. Alexander,
Kampmann Christoph,
Muschol Nicole,
CanaanKühl Sima,
Brand Eva
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1832
Subject(s) - fabry disease , medicine , enzyme replacement therapy , renal function , globotriaosylceramide , observational study , urology , alpha galactosidase , prospective cohort study , gastroenterology , endocrinology , cardiology , disease
Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A (α‐Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α‐Gal A activity. We assessed safety along with cardiovascular, renal, and patient‐reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under “real‐world” conditions. Fifty‐nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (−7.2 and −13.7 g/m 2 , P = 0.0050 and P = 0.0061). FD‐specific manifestations and symptoms remained stable (all P > 0.05). Both sexes presented with a reduction of estimated glomerular filtration rate (secondary end point) (−6.9 and −5.0 mL/minute/1.73 m 2 ; P = 0.0020 and P = 0.0004, respectively), which was most prominent in patients with low blood pressure ( P = 0.0271). α‐Gal A activity increased in male patients by 15% from 29% to 44% of the normal wild‐type activity ( P = 0.0106) and plasma lyso‐Gb3 levels were stable in females and males ( P = 0.3490 and P = 0.2009). Reevaluation of mutations with poor biochemical response revealed no marked activity increase in a zero activity background. We conclude that therapy with migalastat was generally safe and resulted in an amelioration of left ventricular mass. In terms of impaired renal function, blood pressure control seems to be an unattended important goal.