A randomized study of alglucosidase alfa in late-onset Pompe's disease

Ans T. Van Der Ploeg, Paula R. Clemens, Deyanira Corzo, Diana M. Escolar, Julaine Florence, Geert Jan Groeneveld, Serge Herson, Priya S. Kishnani, Pascal Laforet, Stephen L. Lake, Dale J. Lange, Robert T. Leshner, Jill E. Mayhew, Claire Morgan, Kenkichi Nozaki, Dorothy J. Park, Alan Pestronk, Barry Rosenbloom, Alison Skrinar, Carine I. Van CapelleNadine A. Van Der Beek, Melissa Wasserstein, Sasa A. Zivkovic

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Abstract

BACKGROUND: Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease. METHODS: Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC). RESULTS: At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1±13.1 m on the 6-minute walk test and an absolute increase of 3.4±1.2 percentage points in FVC; P = 0.03 and P = 0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients). CONCLUSIONS: In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)

Original languageEnglish
Pages (from-to)1396-1406
Number of pages11
JournalNew England Journal of Medicine
Volume362
Issue number15
DOIs
StatePublished - Apr 15 2010

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    Van Der Ploeg, A. T., Clemens, P. R., Corzo, D., Escolar, D. M., Florence, J., Groeneveld, G. J., Herson, S., Kishnani, P. S., Laforet, P., Lake, S. L., Lange, D. J., Leshner, R. T., Mayhew, J. E., Morgan, C., Nozaki, K., Park, D. J., Pestronk, A., Rosenbloom, B., Skrinar, A., ... Zivkovic, S. A. (2010). A randomized study of alglucosidase alfa in late-onset Pompe's disease. New England Journal of Medicine, 362(15), 1396-1406. https://doi.org/10.1056/NEJMoa0909859