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.