Galafold helps stabilize kidney, heart function in Fabry disease: Study
Therapy also significantly reduced blood levels of disease biomarker
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Oral treatment with Galafold (migalastat) helped keep kidney and heart function largely stable over years of follow-up in adults with Fabry disease, according to a real-world U.K. study.
The therapy also significantly reduced blood levels of lyso-Gb3, a disease biomarker, in both people starting treatment for the first time and those who switched from enzyme replacement therapy (ERT).
Still, some patients experienced complications or side effects that led them to stop treatment, highlighting that responses to Galafold can vary even among people with disease-causing mutations considered amenable to the therapy. Such a finding underscores that “variant amenability alone may not predict clinical benefit,” researchers wrote.
The study, “Effectiveness and tolerability of migalastat in adult Fabry disease: A single regional centre experience,” was published in Molecular Genetics and Metabolism Reports.
Galafold stabilizes faulty forms of key enzyme
Fabry disease is caused by mutations in the GLA gene that lead to a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). As a result, certain fatty substances, mainly globotriaosylceramide (Gb3), accumulate to toxic levels in cells, leading to progressive kidney and heart disease and other Fabry symptoms.
For years, the mainstay of Fabry treatment has been ERT, which provides patients with a lab-made version of alpha-Gal A to help clear Gb3 and its metabolite, lyso-Gb3, from cells. While effective at easing symptoms and slowing disease progression, the need for lifelong intravenous (into-the-vein) infusions has prompted the development of alternative approaches.
One such approach is Galafold, an oral chaperone therapy approved for adults with Fabry disease who carry certain GLA mutations. It works by stabilizing faulty forms of the alpha-Gal enzyme, allowing them to function more effectively within cells. In the U.K., Galafold has been approved since 2016 for people, ages 16 and older, with a confirmed diagnosis of Fabry and an amenable mutation.
Phase 3 clinical trials, including FACETS (NCT00925301) and ATTRACT (NCT01218659), showed that Galafold reduced damage to the kidney and heart and had effects on kidney function comparable to those of ERTs, such as Fabrazyme, for patients with amenable mutations.
“Despite demonstrated efficacy in clinical trials, long-term real-world data remain necessary, particularly in mixed groups of treatment-naïve and ERT-switch patients,” the researchers wrote. They also noted that previous studies included limited genetic data and mostly short-term follow-up.
Galafold generally well-tolerated overall
To learn more, a team of researchers in the U.K. retrospectively analyzed data from 87 adults with Fabry who were treated with Galafold at a single regional center from January 2016 to December 2024.
Participants, including 55 men and 32 women, had a median age of 51. Most (66.7%) carried mutations associated with late-onset disease, while 13.8% carried mutations that cause the classic, more severe form of Fabry.
Among them, 48 had never received Fabry treatment before, and 39 switched from previous ERT. Treatment-naive patients were older overall, with a median age of 57, compared with 47 in the switch group. There were no significant differences in heart disease burden between the two groups at the start of the study. However, patients who switched from ERT had better kidney function, consistent with earlier diagnosis and prior treatment exposure.
Participants were followed for a median of 3.6 years in the treatment-naive group and 11.8 years in the previously treated with ERT group. Before switching to Galafold, the latter group had received ERT for a median of 4.7 years.
Overall, Galafold was generally well tolerated. Six men (6.9%) experienced clinically significant adverse events. One died due to Fabry, and five discontinued Galafold due to worsening heart disease in two cases, declining kidney function in one, gastrointestinal intolerance in another, and rising lyso-Gb3 levels in the last participant despite otherwise stable disease.
Measures of kidney, heart function remained largely stable over time
Among 84 participants with available data, blood levels of lyso-Gb3 declined significantly throughout follow-up. Median levels fell by 55.2% in treatment-naive patients and by 47.2% in those who switched from ERT. About one-third of patients in each group reached normal lyso-Gb3 levels during follow-up.
Measures of kidney and heart function remained largely stable over time. Although the proportion of patients with normal kidney function declined over time in both groups, most maintained near-normal values of glomerular filtration rate — a measure of kidney function — and no patient progressed to end-stage kidney disease. Measures of heart structure and function also remained broadly stable throughout follow-up.
Heart-related complications occurred in 14 treatment-naive patients (29.2%) and 20 patients who switched from ERT (51.3%). However, researchers noted that patients in the switch group were followed for substantially longer periods, which likely contributed to the higher number of events observed.
“These findings emphasise that variant amenability, while necessary, may not be sufficient to predict therapeutic benefit,” the researchers concluded, adding that treatment decisions should still take into account a patient’s specific mutation and disease features “to optimise outcomes and advance precision management in [Fabry disease].”
