Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease

Purpose: A clinical trial was conducted to evaluate the safety and efficacy of alglucosidase alfa in infants and children with advanced Pompe disease.Methods: Open-label, multicenter study of IV alglucosidase alfa treatment in 21 infants 3–43 months old (median 13 months) with minimal acid α-glucosidase activity and abnormal left ventricular mass index by echocardiography. Patients received IV alglucosidase alfa every 2 weeks for up to 168 weeks (median 120 weeks). Survival results were compared with an untreated reference cohort.Results: At study end, 71% (15/21) of patients were alive and 44% (7/16) of invasive-ventilator free patients remained so. Compared with the untreated reference cohort, alglucosidase alfa reduced the risk of death by 79% (P < 0.001) and the risk of invasive ventilation by 58% (P = 0.02). Left ventricular mass index improved or remained normal in all patients evaluated beyond 12 weeks; 62% (13/21) achieved new motor milestones. Five patients were walking independently at the end of the study and 86% (18/21) gained functional independence skills. Overall, 52% (11/21) of patients experienced infusion-associated reactions; 95% (19/20) developed IgG antibodies to recombinant human lysosomal acid α-glucosidase; no patients withdrew from the study because of safety concerns.Conclusions: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival. Treatment also improved indices of cardiomyopathy, motor skills, and functional independence.

[1]  B. Thurberg,et al.  Differential muscular glycogen clearance after enzyme replacement therapy in a mouse model of Pompe disease. , 2007, Molecular genetics and metabolism.

[2]  M. Ausems,et al.  Broad spectrum of Pompe disease in patients with the same c.-32-13T→G haplotype , 2007, Neurology.

[3]  B. Byrne,et al.  Recombinant human acid α-glucosidase , 2007, Neurology.

[4]  B. Byrne,et al.  Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. , 2007, Neurology.

[5]  G. Herman,et al.  Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. , 2006, The Journal of pediatrics.

[6]  P. Doorn,et al.  Pompe disease (glycogen storage disease type II): clinical features and enzyme replacement therapy. , 2006, Acta neurologica Belgica.

[7]  Wuh-Liang Hwu,et al.  A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. , 2006, The Journal of pediatrics.

[8]  T. Voit,et al.  Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial , 2005, Neuromuscular Disorders.

[9]  M. Vogel,et al.  Left ventricular myocardial mass determined by cross-sectional echocardiography in normal newborns, infants, and children , 1991, Pediatric Cardiology.

[10]  S. Haley,et al.  Pediatric physical functioning reference curves. , 2004, Pediatric neurology.

[11]  C. I. Zeeuw,et al.  Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse , 2004, Neurobiology of Disease.

[12]  R. Howell,et al.  Pompe disease in infants and children. , 2004, The Journal of pediatrics.

[13]  W. Hop,et al.  Long-Term Intravenous Treatment of Pompe Disease With Recombinant Human -Glucosidase From Milk , 2004 .

[14]  J. Smeitink,et al.  Enzyme therapy for Pompe disease with recombinant human α-glucosidase from rabbit milk , 2001, Journal of Inherited Metabolic Disease.

[15]  W. Hop,et al.  Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. , 2004, Pediatrics.

[16]  N. Raben,et al.  Enzyme replacement therapy in the mouse model of Pompe disease. , 2003, Molecular genetics and metabolism.

[17]  W. Hop,et al.  The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature. , 2003, Pediatrics.

[18]  S. Haley,et al.  Development of a disease-specific disability instrument for Pompe disease , 2003, Pediatric rehabilitation.

[19]  M. Smrkovsky,et al.  Bayley Scales of Infant Development - Second Edition (BSID-II)) , 2003 .

[20]  N. Raben,et al.  Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[21]  J. Smeitink,et al.  Enzyme therapy for pompe disease with recombinant human alpha-glucosidase from rabbit milk. , 2001, Journal of inherited metabolic disease.

[22]  J. Charrow,et al.  Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial , 2001, Genetics in Medicine.

[23]  J. Darrah,et al.  Motor Assessment of the Developing Infant , 1994 .

[24]  S. Haley,et al.  Concurrent and construct validity of the Pediatric Evaluation of Disability Inventory. , 1990, Physical therapy.

[25]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[26]  D.,et al.  Regression Models and Life-Tables , 2022 .

[27]  PDMS – 2 Peabody Developmental Motor Scales Second Edition , .