@article {Hughes288, author = {Derralynn A Hughes and Kathleen Nicholls and Suma P Shankar and Gere Sunder-Plassmann and David Koeller and Khan Nedd and Gerard Vockley and Takashi Hamazaki and Robin Lachmann and Toya Ohashi and Iacopo Olivotto and Norio Sakai and Patrick Deegan and David Dimmock and Fran{\c c}ois Eyskens and Dominique P Germain and Ozlem Goker-Alpan and Eric Hachulla and Ana Jovanovic and Charles M Lourenco and Ichiei Narita and Mark Thomas and William R Wilcox and Daniel G Bichet and Raphael Schiffmann and Elizabeth Ludington and Christopher Viereck and John Kirk and Julie Yu and Franklin Johnson and Pol Boudes and Elfrida R Benjamin and David J Lockhart and Carrolee Barlow and Nina Skuban and Jeffrey P Castelli and Jay Barth and Ulla Feldt-Rasmussen}, title = {Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study}, volume = {54}, number = {4}, pages = {288--296}, year = {2017}, doi = {10.1136/jmedgenet-2016-104178}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking.Methods The main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously treated with ERT. Effects on heart, disease substrate, patient-reported outcomes (PROs) and safety were also assessed.Results Fifty-seven adults (56\% female) receiving ERT (88\% had multiorgan disease) were randomised (1.5:1), based on a preliminary cell-based assay of responsiveness to migalastat, to receive 18 months open-label migalastat or remain on ERT. Four patients had non-amenable mutant forms of α-Gal based on the validated cell-based assay conducted after treatment initiation and were excluded from primary efficacy analyses only. Migalastat and ERT had similar effects on renal function. Left ventricular mass index decreased significantly with migalastat treatment (-6.6 g/m2 (-11.0 to -2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29\% and 44\% of patients in the migalastat and ERT groups, respectively. Plasma globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat. PROs were comparable between groups. Migalastat was generally safe and well tolerated.Conclusions Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations.Trial registration number: NCT00925301; Pre-results.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/54/4/288}, eprint = {https://jmg.bmj.com/content/54/4/288.full.pdf}, journal = {Journal of Medical Genetics} }