Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-
galactosidase A (α-Gal A) deficiency, which leads to
Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based
therapy for
Fabry disease is
enzyme replacement therapy (ERT) with either
agalsidase alfa (
Replagal) or
agalsidase beta (
Fabrazyme). Based on preclinical data,
migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg
migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected,
intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of
migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of
migalastat HCl and agalsidase. The effects were not related to the administered
migalastat HCl dose, as the 150 mg dose of
migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of
migalastat. No
migalastat HCl-related adverse events or
drug-related tolerability issues were identified.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01196871.