Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with XXXX .

@entity1 @entity2317 @entity8 @entity712 @entity1009 @entity26 @entity591 @entity2314 @entity4346 @entity551
PURPOSE: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly. @entity1 AND METHODS: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-na  ve adults (>= 18 years) with @entity2314 . Inclusion criteria were @entity4346 at baseline, defined as left ventricular mass indexed to height >50 g/m(2.7) for males and >47 g/m(2.7) for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak @entity26 consumption, 6-minute walk test, Minnesota Living with @entity712 Questionnaire, New York Heart Association classification), renal (Modification of Diet in @entity8 , estimated glomerular filtration rate), and biomarker (plasma @entity2317 ) assessments. Safety endpoints were adverse events and anti-agalsidase alfa antibodies. RESULTS: Twenty @entity1 were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m(2.7) and 0.5 g/m(2.7), with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak @entity26 consumption, 6-minute walk test, or Minnesota Living with @entity712 Questionnaire. Two @entity1 in each group improved by >= 1 New York Heart Association classification. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (-1.21 mL/ @entity1009 .73 m(2) vs -3.32 mL/ @entity1009 .73 m(2)) or plasma @entity2317 (-1.05 nmol/mL vs -2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the 0.2-mg/kg EOW and weekly groups. @entity591 , fatigue, and @entity551 were experienced by two or more patients overall. Anti-agalsidase alfa antibodies were detected in 11.4% of @entity1 and neutralizing antibodies in 6.8%. Infusion-related reactions did not appear to be correlated with antibody status. CONCLUSION: No efficacy or safety differences were found when the approved EOW dosage of agalsidase alfa was increased to weekly administration. Exploratory analyses for 0.4 mg/kg weekly showed similar results.
