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.

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.

• Authors: Si Houn Hahn, David Kronn, Nancy D Leslie, Loren D M Pena, Pranoot Tanpaiboon, Michael J Gambello, James B Gibson, Richard Hillman, David W Stockton, John W Day, Raymond Y Wang, Kristina An Haack, Raheel Shafi, Susan Sparks, Yang Zhao, Catherine Wilson, Priya S Kishnani, Pompe ADVANCE Study Consortium
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 20 Issue 10 Pg. 1284-1294 (10 2018) ISSN: 1530-0366 [Electronic] United States
• PMID: 29565424 (Publication Type: Clinical Trial, Phase IV, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• GAA protein, human
• alpha-Glucosidases

Topics

• Age of Onset
• Child
• Child, Preschool
• Dose-Response Relationship, Drug
• Female
• Glycogen Storage Disease Type II (drug therapy, genetics, pathology)
• Humans
• Infant
• Infant, Newborn
• Kaplan-Meier Estimate
• Male
• Recombinant Proteins (administration & dosage, adverse effects)
• alpha-Glucosidases (administration & dosage, adverse effects)