Efficacy and safety of migalastat in a Japanese population: a subgroup analysis of the ATTRACT study

Ichiei Narita, Toya Ohashi, Norio Sakai, Takashi Hamazaki, Nina Skuban, Jeffrey P Castelli, Hjalmar Lagast, Jay A Barth, Ichiei Narita, Toya Ohashi, Norio Sakai, Takashi Hamazaki, Nina Skuban, Jeffrey P Castelli, Hjalmar Lagast, Jay A Barth

Abstract

Background: Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis of the global phase III ATTRACT study, the efficacy and safety of oral migalastat, a pharmacologic chaperone, were investigated in Japanese patients with Fabry disease.

Methods: Patients were randomly assigned to receive migalastat (150 mg every other day) or to continue biweekly enzyme replacement therapy infusions (ERT; agalsidase alfa 0.2 mg/kg or agalsidase beta 1.0 mg/kg) for 18 months followed by a 12-month open-label extension during which all patients received migalastat. End points included glomerular filtration rate (estimated and measured), left ventricular mass index (LVMi), composite clinical outcomes, leukocyte alpha-galactosidase A activity, plasma globotriaosylsphingosine (lyso-Gb3), and safety.

Results: Data from 7 Japanese patients (migalastat, 5; ERT, 2), mean age 55 years, with high disease burden, were analyzed. All patients in the migalastat group completed the open-label comparison and extension periods. At 18 months, efficacy in the Japanese patient population was similar to that in the overall ATTRACT population. Migalastat treatment increased leukocyte alpha-galactosidase A activity, stabilized renal function, and decreased LVMi. Plasma lyso-Gb3 levels remained low and stable. Additionally, the long-term extension study showed that efficacy of migalastat was maintained for up to 48 months. Migalastat was safe and well tolerated in the Japanese patients, as in the overall ATTRACT population.

Conclusion: Migalastat can be used to treat Japanese patients with Fabry disease with GLA mutations amenable to migalastat according to the dosage and administration approved in other countries.

Trial registration numbers: ClinicalTrials.gov, NCT01218659 and NCT02194985.

Keywords: Alpha-galactosidase; Enzyme replacement therapy; Fabry disease; Migalastat; Mutation; Pharmacologic chaperone.

Conflict of interest statement

Employment: Nina Skuban, Jeffrey P. Castelli, Hjalmar Lagast, and Jay A. Barth (Amicus Therapeutics Inc.); stock ownership or options: Nina Skuban, Jeffrey P. Castelli, Hjalmar Lagast, and Jay A. Barth (Amicus Therapeutics Inc.); research grant: Toyo Ohashi (ARVOBIO Inc., Dainippon Sumitomo Pharma, Sanofi Genzyme, Amicus Therapeutics Inc.) and Noroi Sakai (Sanofi Genzyme, Dainippon Sumitomo Pharma); Honoraria: Toyo Ohashi (Dainippon Sumitomo Pharma) and Norio Sakai (Sanofi Genzyme, Dainippon Sumitomo Pharma). All other authors have declared that no conflict of interest exists.

Figures

Fig. 1
Fig. 1
Patient flowchart: ATTRACT study. ERT enzyme replacement therapy
Fig. 2
Fig. 2
Annualized rate of change in the glomerular filtration rate (mL/min/1.73 m2). a Annualized rate of change of eGFRCKD-EPI from baseline to month 18. Dots are individual patient data. b Annualized rate of change of eGFRCKD-EPI from baseline to month 48 in the 5 Japanese patients randomly assigned to the migalastat group at study entry. Because 1 patient was withdrawn from the study by the investigator at month 30 or thereafter, data for month 42 and month 48 are from the remaining 4 patients. Blue line is mean change from baseline; remaining lines represent individual patient data. c Annualized rate of change of mGFRiohexol from baseline to month 18. eGFRCKD-EPI estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration equation, ERT enzyme replacement therapy, mGFRiohexol estimated glomerular filtration rate determined from clearance of iohexol, N/A not applicable, SD standard deviation
Fig. 2
Fig. 2
Annualized rate of change in the glomerular filtration rate (mL/min/1.73 m2). a Annualized rate of change of eGFRCKD-EPI from baseline to month 18. Dots are individual patient data. b Annualized rate of change of eGFRCKD-EPI from baseline to month 48 in the 5 Japanese patients randomly assigned to the migalastat group at study entry. Because 1 patient was withdrawn from the study by the investigator at month 30 or thereafter, data for month 42 and month 48 are from the remaining 4 patients. Blue line is mean change from baseline; remaining lines represent individual patient data. c Annualized rate of change of mGFRiohexol from baseline to month 18. eGFRCKD-EPI estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration equation, ERT enzyme replacement therapy, mGFRiohexol estimated glomerular filtration rate determined from clearance of iohexol, N/A not applicable, SD standard deviation
Fig. 3
Fig. 3
Change in LVMi (g/m2) from baseline to month 30 in Japanese patients who received migalastat. LVMi data are from 5 Japanese patients who were randomly assigned to migalastat in the ATTRACT study and then enrolled in AT1001-042 OLE study. Blue line is mean change from baseline; remaining lines represent individual patient data. LVMi left ventricular mass index, N/A not applicable, OLE open-label extension, SD standard deviation

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