Abstract for presentation at 11th International Congress of Human Genetics

Early signs of benefit in children with late-onset Pompe disease following the first 6 months of treatment with enzyme replacement therapy (recombinant human acid α-glucosidase) in an open-label study

  • Dr Ans van der Ploeg, Division of Metabolic Diseases and Genetics, Department of Paediatrics, Sophia Children's Hospital, Rotterdam , The Netherlands, The Netherlands
  • Prof Arnold Reuser, Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands, The Netherlands
  • Dr Carine van Capelle, Division of Metabolic Diseases and Genetics, Department of Paediatrics, Sophia Children's Hospital, Rotterdam , The Netherlands, The Netherlands

    • Introduction: Pompe disease is a rare metabolic myopathy caused by a deficiency of the intra-lysosomal enzyme acid α-glucosidase (GAA) leading to a clinical spectrum of disease with onset from early infancy to late adulthood. The benefits of recombinant human acid alpha glucosidase (rhGAA) on cardiac, respiratory and skeletal muscle have been demonstrated in clinical studies evaluating Pompe patients with onset of disease in early infancy. The natural course of patients with a later onset of symptoms is typically one of progressive respiratory and skeletal muscle weakness (but no primary cardiac involvement) ultimately leading to ventilator and/or wheelchair-dependency.
    Methods: The safety and efficacy of rhGAA 20 mg/kg qow i.v. was evaluated in 5 (3 male/2 female) Caucasian patients (aged 5-15 years at treatment onset) with a confirmed diagnosis of Pompe disease in an open-label study. At Baseline, all patients were ambulatory and one required nocturnal non-invasive ventilation.
    Results: Early signs of clinical benefit on respiratory and motor function were apparent following the first 6 months of treatment compared to Baseline, as indicated by a clinically meaningful (>11%) increase in % predicted forced vital capacity (FVC) in 3 patients (2 had FVC < 80% predicted at Baseline) as well as a clinically meaningful increase (> 37 metres) in the distance walked in 6 minutes (conducted at fast speed) in 3 patients. rhGAA was well tolerated by all patients and no infusion-associated reactions were observed. Four patients developed anti-rhGAA IgG antibodies (titers ranging from 1/100 to 1/800) between weeks 8 and 16 with no signs of an (in-vitro) inhibitory antibody effect.
    Conclusion: Administration of rhGAA to patients with later onset of symptoms of Pompe disease was well tolerated and led to early signs of benefit on skeletal and respiratory muscle function in the first 6 months of treatment.

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