Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

Abstract

OBJECTIVE:

To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.

STUDY DESIGN:

We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use, echocardiograms, growth, and motor and cognitive function.

RESULT:

After 52 weeks of treatment, 6 of 8 patients were alive, and 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated; no death was drug-related.

CONCLUSION:

rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.

• Authors: Priya Sunil Kishnani, Marc Nicolino, Thomas Voit, R Curtis Rogers, Anne Chun-Hui Tsai, John Waterson, Gail E Herman, Andreas Amalfitano, Beth L Thurberg, Susan Richards, Mark Davison, Deyanira Corzo, Y T Chen
• Journal: The Journal of pediatrics (J Pediatr) Vol. 149 Issue 1 Pg. 89-97 (Jul 2006) ISSN: 0022-3476 [Print] United States
• PMID: 16860134 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Glycogen
• GAA protein, human
• alpha-Glucosidases

Topics

• Body Height (drug effects)
• Body Weight (drug effects)
• Cardiomyopathy, Hypertrophic (drug therapy, etiology)
• Child Development
• Europe (epidemiology)
• Female
• Glycogen (metabolism)
• Glycogen Storage Disease Type II (complications, drug therapy, mortality)
• Hearing Disorders (etiology)
• Humans
• Infant
• Infant, Newborn
• Infusions, Intravenous
• Male
• Muscle Hypotonia (drug therapy, etiology)
• Muscle, Skeletal (metabolism, pathology)
• Respiration, Artificial
• Treatment Outcome
• United States (epidemiology)
• alpha-Glucosidases (metabolism, therapeutic use)