Clinical Benefit Following Enzyme Replacement Therapy (ERT) with Alglucosidase alpha in Children with Pompe Disease. D. Corzo¹, C. Spencer², B. Byrne², M. Nicolino³, W.L. Hwu⁴, N. Leslie⁵, H. Mandel⁶, E. Wraith⁷, P. Kishnani⁸. 1) Genzyme Corp, Cambridge, MA; 2) Shands Hospital at the University of Florida College of Medicine, Gainsville, FL; 3) University Hospital Debrousse, Lyon, France; 4) National Taiwan University Hospital, Taipei, Taiwan; 5) Cincinnati Children's Hospital, Cincinnati, OH; 6) Ramban Medical Center, Haifa, Israel; 7) Royal Manchester Children's Hospital, Manchester, UK; 8) Duke University Medical Center, Durham, NC.
   Introduction. Pompe is a metabolic myopathy due to a deficiency of the lysosomal enzyme acid alpha glucosidase. Those with onset of symptoms in the first year of life typically die from cardiac and respiratory failure at a median age of 8.7 months (Kishnani et al., in press). Methods. Study 1 enrolled 18 patients <6 months of age; Study 2 enrolled 21 patients >6 to 36 months of age. All patients had onset of symptoms in the first year of life and evidence of cardiomyopathy prior to treatment. Results. After 1 year of ERT with rhGAA 18/18 (100%) patients in Study 1 were alive and 15/18 patients (83%) were free of invasive-ventilator support. In Study 2, 16/21 patients (76%) were alive and 11/16 (69%) patients who were free of invasive ventilation at baseline, remained so. All but 2 patients with follow up cardiac echo data demonstrated decrease in LV mass; 2 patients showed LV mass stabilization. Thirteen out of 15 patients (73%) of patients treated at <6 months of age (Study 1) showed acquisition of new motor milestones, in contrast to10/21 patients (48%) of those treated at >6 months of age (Study 2). Thirty five out of 39 patients (90%) developed anti-rhGAA antibodies; in one case antibodies had inhibitory activity (in vitro). Conclusions. Administration of alglucosidase alpha to this large cohort of patients with Pompe disease resulted in measurable clinical benefit, even in those patients with advanced stage of the disease at onset of ERT (Study 2). Results from these trials provide further evidence that early initiation of ERT is of paramount importance to maximize the chances of a favorable motor outcome. Patients continue to be treated and followed up in extension studies.