Switching from enzyme replacement therapy (ERT) to Galafold (migalastat) is a valid and safe therapeutic option for Fabry disease patients with Galafold-amenable mutations, according to a real-life study from Italy.
Notably, the data showed that Galafold resulted in greater and significant improvements in patients’ heart size and kidney function, compared with ERT.
Nevertheless, larger and longer studies are needed to confirm these findings, the researchers noted.
The study, “Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data,” was published in the European Journal of Human Genetics.
Fabry disease is caused by mutations in the GLA gene, which result in absent or markedly reduced activity of the alpha-galactosidase A (Gal A) enzyme. This deficiency leads to the damaging buildup of two fat molecules — Gb3 and lyso-Gb3 — in tissues and organs such as the heart, kidneys, nervous system, eyes, and skin.
Galafold, developed by Amicus Therapeutics, is an oral chaperone therapy that restores the activity of certain unstable forms of Gal A, referred to as “amenable.” It is estimated that 35–50% of all Fabry patients worldwide have Galafold-amenable mutations.
As the only oral therapy approved for Fabry disease, Galafold (taken every other day) may reduce the burden of lifelong, into-the-vein infusions of ERT — Fabrazyme (agalsidase beta) or Replagal (agalsidase alfa) — every two weeks. ERT, which has been the mainstay of Fabry disease treatment, involves the delivery of a lab-made version of Gal A to patients.
Galafold’s use also avoids frequent adverse and immune reactions associated with ERT infusions and has been suggested to result in more stable Gal A activity than ERT.
While Galafold’s safety and effectiveness are well-established, data on the effects of switching from ERT to Galafold remain limited.
To fill this gap, researchers in Italy compared the safety and effectiveness of ERT and Galafold in seven adult men (ages 18–66) with Fabry disease and Galafold-amenable mutations who underwent such treatment switch.
Participants, five with classic disease and two with late-onset disease, were recruited at the University Hospital Federico II of Naples, in Italy. They received at least one year of stable ERT (six on Replagal and one on Fabrazyme) before switching to Galafold without any interval and were prospectively followed for 12 months after treatment switch.
A complete clinical assessment was performed in all participants at each visit. This included an evaluation of patients’ heart, kidneys, and nervous system functions, Fabry disease-related symptoms, quality of life, Gal A activity, lyso-Gb3 blood levels, and side effects.
Results showed that the parameters of heart, kidney, and neurologic function in these men remained stable after they switched to Galafold, except for the left ventricular mass index (a measure of heart size) and protein levels in the urine (a marker of kidney dysfunction), which were reduced significantly.
These findings suggested that Galafold significantly improved patients’ heart and kidney health, compared with ERT.
In addition, the two men who complained of pain before initiating ERT reported an even further easing of such symptoms with Galafold. Other Fabry-related symptoms, as well as quality of life, remained stable.
Compared with baseline (before any treatment), there was a significant increase in Gal A activity and a significant drop in lyso-Gb3 blood levels after one year of Galafold, suggesting a sustained disease stability. The levels of lyso-Gb3 after one year of either treatment were not significantly different. Gal A activity after ERT was not reported.
Moreover, Galafold was generally safe and well-tolerated, with the same number of patients reporting side effects as those under ERT (two patients, 28%). Notably, ERT-related side effects were resolved with the switch to Galafold, while two men experienced treatment-related side effects only with Galafold. Most side effects were mild in severity and none led to treatment discontinuations.
“In conclusion, in Fabry patients with amenable mutations, switching from ERT … to the pharmacological chaperone [Galafold] seems to be valid, safe and well tolerated,” the researchers wrote.
They emphasized, however, that larger, multi-center studies with longer follow-up periods are needed to confirm these findings.
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