Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.

Abstract

Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy.

• Authors: Laura E Case, Carl Bjartmar, Claire Morgan, Robin Casey, Joel Charrow, John P Clancy, Majed Dasouki, Stephanie DeArmey, Khan Nedd, Mary Nevins, Heidi Peters, Dawn Phillips, Zachary Spigelman, Cynthia Tifft, Priya S Kishnani
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 25 Issue 4 Pg. 321-32 (Apr 2015) ISSN: 1873-2364 [Electronic] England
• PMID: 25617983 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Immunoglobulin G
• Neuromuscular Agents
• GAA protein, human
• alpha-Glucosidases

Topics

• Adolescent
• Adult
• Age of Onset
• Child
• Child, Preschool
• Cohort Studies
• Enzyme Replacement Therapy (adverse effects, methods)
• Female
• Glycogen Storage Disease Type II (drug therapy, physiopathology)
• Humans
• Immunoglobulin G (blood)
• Infant
• Male
• Middle Aged
• Motor Skills (drug effects)
• Neuromuscular Agents (adverse effects, therapeutic use)
• Random Allocation
• Treatment Outcome
• Young Adult
• alpha-Glucosidases (adverse effects, therapeutic use)