Abstract

PurposePompe disease results from lysosomal acid a-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.MethodsA 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.ResultsWeek 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.ConclusionsMost Pompe disease patients were clinically stable/improved after transitioning to 4,000?L rhGAA. Safety profiles of both rhGAA forms were consistent.Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.2.

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