Recombinant human acid α-glucosidase: Major clinical benefits in infantile-onset Pompe disease
Journal
Neurology
Journal Volume
68
Journal Issue
2
Pages
99-109
Date Issued
2007
Author(s)
Kishnani P.S.
Corzo D.
Nicolino M.
Byrne B.
Mandel H.
Leslie N.
Levine J.
Spencer C.
McDonald M.
Li J.
Dumontier J.
Halberthal M.
Hopkin R.
Vijayaraghavan S.
Gruskin D.
Bartholomew D.
Van Der Ploeg A.
Clancy J.P.
Parini R.
Morin G.
Beck M.
De La Gastine G.S.
Jokic M.
Thurberg B.
Richards S.
Bali D.
Davison M.
Worden M.A.
Chen Y.T.
Wraith J.E.
Abstract
BACKGROUND: Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid α-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and early death. The safety and efficacy of recombinant human (rh) GAA were evaluated in 18 patients with rapidly progressing infantile-onset Pompe disease. METHODS: Patients were diagnosed at 6 months of age and younger and exhibited severe GAA deficiency and cardiomyopathy. Patients received IV infusions of rhGAA at 20 mg/kg (n = 9) or 40 mg/kg (n = 9) every other week. Analyses were performed 52 weeks after the last patient was randomized to treatment. RESULTS: All patients (100%) survived to 18 months of age. A Cox proportional hazards analysis demonstrated that treatment reduced the risk of death by 99%, reduced the risk of death or invasive ventilation by 92%, and reduced the risk of death or any type of ventilation by 88%, as compared to an untreated historical control group. There was no clear advantage of the 40-mg/kg dose with regard to efficacy. Eleven of the 18 patients experienced 164 infusion-associated reactions; all were mild or moderate in intensity. CONCLUSIONS: Recombinant human acid α-glucosidase is safe and effective for treatment of infantile-onset Pompe disease. Eleven patients experienced adverse events related to treatment, but none discontinued. The young age at which these patients initiated therapy may have contributed to their improved response compared to previous trials with recombinant human acid α-glucosidase in which patients were older. ?2007AAN Enterprises, Inc.
SDGs
Other Subjects
recombinant enzyme; recombinant glucan 1,4 alpha glucosidase; unclassified drug; abnormal respiratory sound; adult; agitation; article; artificial ventilation; cardiomyopathy; clinical article; controlled study; coughing; cyanosis; death; disease severity; drug effect; drug efficacy; drug eruption; drug fatality; drug safety; erythema; female; fever; flushing; gastroesophageal reflux; glycogen storage disease type 2; heart rate; human; human cell; induced hypotension; irritability; livedo reticularis; male; mortality; oxygen saturation; pallor; priority journal; proportional hazards model; pruritus; restlessness; retching; rigor; risk assessment; risk reduction; side effect; tachycardia; tachypnea; treatment outcome; tremor; urticaria; vomiting
Publisher
Lippincott Williams and Wilkins
Type
journal article