Si Houn Hahn1, David Kronn2, Nancy D Leslie3, Loren D M Pena4, Pranoot Tanpaiboon5, Michael J Gambello6, James B Gibson7, Richard Hillman8, David W Stockton9, John W Day10, Raymond Y Wang11,12, Kristina An Haack13, Raheel Shafi13, Susan Sparks13, Yang Zhao13, Catherine Wilson13, Priya S Kishnani14. 1. Departments of Pediatrics and Medicine and Biochemical Genetics Program, Seattle Children's Hospital/University of Washington, Seattle, Washington, USA. sihoun.hahn@seattlechildrens.org. 2. Pediatrics, New York Medical College, Valhalla, New York, USA. 3. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 4. Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. 5. Genetics, Children's National Health System, Washington, DC, USA. 6. Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA. 7. Clinical and Metabolic Genetics, Dell Children's Medical Group, Austin, Texas, USA. 8. Professor Emeritus, University of Missouri Child Health, Columbia, Missouri, USA. 9. Division of Genetic, Genomic, and Metabolic Disorders, Wayne State University and Children's Hospital of Michigan, Detroit, Michigan, USA. 10. Neurology, Pediatrics, and Medical Genetics, Stanford University, Stanford, California, USA. 11. Lysosomal Storage Disease Program, Children's Hospital of Orange County, Orange, California, USA. 12. Pediatrics, University of California-Irvine School of Medicine, Orange, California, USA. 13. Sanofi Genzyme, Cambridge, Massachusetts, USA. 14. Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. priya.kishnani@duke.edu.
Abstract
PURPOSE: Pompe disease results from lysosomal acid α-glucosidase (GAA) deficiency and its associated glycogen accumulation and muscle damage. Alglucosidase alfa (recombinant human GAA (rhGAA)) received approval in 2006 as a treatment for Pompe disease at the 160 L production scale. In 2010, larger-scale rhGAA was approved for patients up to 8 years old without cardiomyopathy. NCT01526785 evaluated 4,000 L rhGAA efficacy/safety in US infantile- or late-onset Pompe disease (IOPD, LOPD) patients up to 1 year old transitioned from 160 L rhGAA. METHODS: A total of 113 patients (87 with IOPD; 26 with LOPD) received 4,000 L rhGAA for 52 weeks dosed the same as previous 160 L rhGAA. Efficacy was calculated as the percentage of patients stable/improved at week 52 (without death, new requirement for invasive ventilation, left ventricular mass z-score increase >1 if baseline was >2, upright forced vital capacity decrease ≥15% predicted, or Gross Motor Function Measure-88 decrease ≥8 percentage points). Safety evaluation included an extension ≤20 months. RESULTS: Week 52 data was available for 104 patients, 100 of whom entered the extension. At week 52, 87/104 (83.7%) were stable/improved. Overall survival was 98.1% overall, 97.6% IOPD, 100% LOPD; 92.4% remained invasive ventilator-free (93.4% IOPD, 88.7% LOPD). Thirty-five patients had infusion-associated reactions. Eight IOPD patients died of drug-unrelated causes. CONCLUSIONS: Most Pompe disease patients were clinically stable/improved after transitioning to 4,000 L rhGAA. Safety profiles of both rhGAA forms were consistent.
PURPOSE: Pompe disease results from lysosomal acid α-glucosidase (GAA) deficiency and its associated glycogen accumulation and muscle damage. Alglucosidase alfa (recombinant human GAA (rhGAA)) received approval in 2006 as a treatment for Pompe disease at the 160 L production scale. In 2010, larger-scale rhGAA was approved for patients up to 8 years old without cardiomyopathy. NCT01526785 evaluated 4,000 L rhGAA efficacy/safety in US infantile- or late-onset Pompe disease (IOPD, LOPD) patients up to 1 year old transitioned from 160 L rhGAA. METHODS: A total of 113 patients (87 with IOPD; 26 with LOPD) received 4,000 L rhGAA for 52 weeks dosed the same as previous 160 L rhGAA. Efficacy was calculated as the percentage of patients stable/improved at week 52 (without death, new requirement for invasive ventilation, left ventricular mass z-score increase >1 if baseline was >2, upright forced vital capacity decrease ≥15% predicted, or Gross Motor Function Measure-88 decrease ≥8 percentage points). Safety evaluation included an extension ≤20 months. RESULTS: Week 52 data was available for 104 patients, 100 of whom entered the extension. At week 52, 87/104 (83.7%) were stable/improved. Overall survival was 98.1% overall, 97.6% IOPD, 100% LOPD; 92.4% remained invasive ventilator-free (93.4% IOPD, 88.7% LOPD). Thirty-five patients had infusion-associated reactions. Eight IOPD patients died of drug-unrelated causes. CONCLUSIONS: Most Pompe disease patients were clinically stable/improved after transitioning to 4,000 L rhGAA. Safety profiles of both rhGAA forms were consistent.
Entities:
Keywords:
acid maltase deficiency; alglucosidase alfa; glycogen storage disease type 2; glycogenosis type 2; recombinant human acid α-glucosidase
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