A recent post hoc analysis of long-term efficacy of migalastat in females with Fabry disease was published in the Journal of Medical Genetics.
Fabry disease is a rare lysosomal storage disease characterized by a deficiency of the enzyme alpha-galactosidase (alpha-GAL). Alpha-GAL helps break down a fatty acid called globotriaosylceramide (GL3) and without enough, the lysosomes become filled with GL3 and can not work well. Symptoms of Fabry disease may include episodes of pain, especially in the hands and feet, angiokeratomas, hypohidrosis, corneal opacity, and hearing loss. Internal organs, such as the kidney, heart, or brain, may also be affected, leading to progressive kidney damage, heart attacks, and strokes. Fabry disease is an X-linked genetic disease due to changes in the GLA gene. Since it is X-linked, physicians have long thought females with Fabry disease are less impacted by the condition, but that is not necessarily the case.
The FACETS (NCT00925301) clinical trial was a double-blind, placebo-controlled study comparing the effect of migalastat versus placebo on kidney globotriaosylceramide in patients with Fabry disease. The ATTRACT (NCT01218659) clinical trial was a phase 3, randomized, open-label, active-controlled study evaluating the safety and efficacy of 150 mg of migalastat once every other day and enzyme replacement therapy in patients with Fabry disease. Both male and female patients were enrolled in the studies.
The goal of this post hoc analysis was to assess baseline characteristics and long-term efficacy of migalastat regarding cardiac and renal function and Fabry-associated clinical events (FACEs) in females with Fabry disease. Migalastat is a chaperone therapy that stabilizes and facilitates trafficking of amenable mutant forms of alpha-GAL enzyme from the endoplasmic reticulum to lysosomes and increases lysosomal activity.
A total of 60 female patients had a median migalastat exposure of 5.1 years. At baseline, the median age was 47 years, 70% had multiorgan involvement, and 21.7% had left ventricular hypertrophy (LVH). In multiorgan involvement and LVH subgroups, the median baseline estimated glomerular filtration rate (eGFR) was in chronic kidney disease stage 2. Annualized rate of change in left ventricular mass index remained below 1 g/m2/year regardless of LVH or eGFR category at baseline.
Mean eGFR annualized change was -1.1 mL/min/1.73 m2 overall. Ten FACEs were reported in eight patients, seven of whom had prior events. Seven were cardiac and three were cerebrovascular transient ischaemic attacks. The incidence of renal, cardiac, and cerebrovascular events were 0, 24.9, and 10.7 events per patient-years, respectively.
This data highlights the disease severity and burden of females with Fabry disease and supports the long-term efficacy of migalastat.
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To learn more about Fabry disease and other rare lysosomal conditions, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
