A Phase 4 Prospective Study in Patients with Adult Pompe Disease Treated with Alglucosidase Alfa.

s S73 marker of disease activity, was abnormally elevated (>39 ms) in approximately 1/3 of all muscles. No changes were observed from baseline on MRI parameters. Mean increase from baseline in the 6MWT was 37.3 meters (p = 0.02). Eleven patients improved; 4 patients worsened. Mean improvement from baseline in percent predicted FVC was 1.8% (p = 0.67). Seven patients improved; 8 patients worsened. No deaths or discontinuations due to AEs occurred. Fifteen patients (93.8%) reported at least one AE for a total of 90 events. The majority were infusion-associated reactions. Overall, this was consistent with the known safety profi le for alglucosidase alfa. This study provides the fi rst histopathological support for the expected biological activity of alglucosidase alfa in adult Pompe disease. Alglucosidase alfa reduced lysosomal glycogen, with cytoplasmic glycogen remaining. This treatment effect was associated with overall stabilization/improvement on functional assessments. stable (mean: 3.1%; p = 0.19). In 9/10 deltoid biopsies, glycogen was reduced or remained stable (mean: 1.4%; p = 0.01). At baseline, glycogen was present within lysosomes and as free cytoplasmic glycogen outside lysosomes. Histopathology demonstrated post-treatment glycogen was predominantly in cytoplasm. Secondary changes were limited to occasional foci of autophagic debris. No fi brosis, infl ammation, or fatty replacement was observed. Biopsies were MRI guided to enhance sampling from normal appearing muscle. The overall Mercuri score indicated mild muscle involvement, ranging from normal to moderate for individual patients. The upper leg (mean: 1.9; range: 1–3.5) was generally more affected than the lower leg (mean: 1.0; range: 1–1.2). Muscular fatty infi ltration was quantifi ed from a 3-point 3D Dixon acquisition (n = 5). Percent fatty infi ltration was normal or elevated (>10%) and in accordance with the Mercuri scoring degree. Muscle water T2, a Study sponsored by Genzyme, a Sanofi Company