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

Abstract

Background Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis of the global phase III ATT RAC T 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-Gb 3 ), 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 ATT RAC T population. Migalastat treatment increased leukocyte alpha-galactosidase A activity, stabilized renal function, and decreased LVMi. Plasma lyso-Gb 3 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 ATT RAC T 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.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Biomarkers for Monitoring Renal Damage Due to Fabry Disease in Patients Treated with Migalastat: A Review for Nephrologists

“…MEDLINE = Total n = 11, post analysis n = 2 [ 18 , 19 ]; 3 studies were excluded because they were preliminary reports of other studies [ 22 , 24 , 25 ]; 4 studies were excluded because they were sub-analysis of other studies [ 23 , 26 , 27 , 28 ] and 2 studies were excluded because they did not meet the inclusion criteria [ 29 , 30 ]. EMBASE = Total n = 0; SCOPUS = Total n = 0, Cochrane Total n = 0 and Google Academic = Total n = 191, post analysis n = 2 [ 20 , 21 ]; (11 studies were overlapped with MEDLINE, both included and excluded; 1 study was excluded because it was a preliminary report of other study [ 25 ], 1 study was excluded because it did not have renal biomarkers among its dependent variables [ 31 ]; 1 study was excluded because its sub-analysis of other studies [ 32 ]; 173 studies were excluded for not meeting inclusion criteria).…”

Fabry Nephropathy in a Young Female Patient Presenting with Only Urinary Mulberry Bodies Treated with Chaperone Therapy

“…Left ventricular mass has been shown to be an important parameter for assessing the cardiac effects of the treatment in patients with FD [ 15 ]. Male patients with FD receiving PCT had an increase in leukocyte α-Gal A activity, while this was not confirmed in female patients with FD [ 16 ]. Therefore, it could be meaningful to measure the change in enzyme activity in WBC for monitoring the therapeutic effect of PCT in patients with FD.…”

Brazilian consensus recommendations for the diagnosis, screening, and treatment of individuals with fabry disease: Committee for Rare Diseases - Brazilian Society of Nephrology/2021

“…The FACET study reported a decrease greater than 50% in interstitial inclusions in peritubular capillaries, a significant reduction in podocyte inclusions, and improved kidney function, regardless of baseline urinary protein levels, after six months of treatment 91 . In the ATTRACT randomized trial, migalastat and ERT had similar effect over kidney function 18 months into the study 92 , although migalastat increased α-GAL activity, stabilized kidney function, and kept plasma lyso-GL3 levels low in a subgroup of Japanese patients 93 . Another study also observed a decrease in podocyte deposits of GL3 after six months of treatment with migalastat 94 .…”