Fabry Disease
Fabry Disease is a rare lysosomal storage condition. Mutations in the GLA gene cause a type of fat called globotriaosylceramide to build up in the body’s cells. Symptoms range in severity but may include cloudy vision, tinnitus, acroparesthesias, angiokeratomas, hypohidrosis, or gastrointestinal issues. The most severe symptoms can result in life-threatening strokes, heart attacks, and kidney damage. Fabry Disease typically affects males more than females.
The current standard treatment for Fabry Disease is enzyme replacement therapy (ERT). Intravenous infusions provide patients with healthy enzymes to replace the defective ones. This therapy must be completed biweekly for the extent of the patient’s life which can be extremely burdensome. Additionally, unfortunately, the success of ERT varies by patient depending on the severity of their condition and how much organ damage has already been done by the disease.
Two recent Phase 3 clinical trials have shown promise for a new therapy which could aid patients at all levels of disease severity.
Clinical Trials
The first Phase 3 study was titled FACETS. It aimed to evaluate the safety and efficacy of AT1001, or Galafold, compared to placebo. The second study was titled ATTRACT. It utilized the same participants as the FACETS trial, but compared their outcomes to patients who did not have the classic manifestation of the disease (which is the most severe form). Specifically, the ATTRACT trial included 14 males with the condition, 4 males with the non-classic form of the disease, and 32 females.
Instead of replacing the impaired enzyme, Galafold is an oral therapy that works to re-stabilize the dysfunctional enzyme and restore its proper activity. To assess the efficacy of Galafold, researchers examined the function of patient’s hearts, kidneys, and GI tract during 24 months of treatment with Galafold.
At the 6 month mark, those on placebo who had the classic form of the disease were found to be suffering from increased deposits of GL-3 in their kidneys. These patients were then switched to treatment with Galafold, and the deposits subsequently decreased.
At the 24 month mark, those with the most severe form of the condition experienced stabilized kidney function, GI tract improvement, lowered plasma levels of lyso-Gb3, and a decrease in heart size.
Ultimately this trial concluded that Galafold holds the most promise for male patients who have the classic, and most severe form of the disease. However, it will provide benefits for patients with any manifestation of the condition.
The findings from this study were published in the journal, Genetics in Medicine.
You can read more about these clinical trials for Fabry Disease here.
