Efficacy, safety profile, and immunogenicity of alglucosidase alfa produced at the 4, 000-liter scale in US children and adolescents with Pompe disease: ADVANCE, a phase IV, open-label, prospective study. (October 2018)

• Record Type: Journal Article
• Authors: Hahn, Si Houn; Kronn, David; Leslie, Nancy; Pena, Loren; Tanpaiboon, Pranoot; Gambello, Michael; Gibson, James; Hillman, Richard; Stockton, David; Day, John; Wang, Raymond; An Haack, Kristina; Shafi, Raheel; Sparks, Susan; Zhao, Yang; Wilson, Catherine; Kishnani, Priya
• Is Part Of: Genetics in medicine. Volume 20:Number 10(2018)
• Page Start: 1284
• Page End: 1294
• Publication Date: 2018-10
• Subjects: acid maltase deficiency -- alglucosidase alfa -- glycogenosis type 2 -- glycogen storage disease type 2 -- recombinant human acid α-glucosidase; Medical genetics -- Periodicals; Genetic disorders -- Periodicals; 616.04205
• DOI: 10.1038/gim.2018.2
• Languages: English
• ISSNs: 1098-3600

Abstract

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 massz -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.