NEJM -- A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease

Volume 362:1396-1406 April 15, 2010 Number 15
A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease

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

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 [ClinicalTrials.gov] .)



Source Information

From the Departments of Pediatrics, Internal Medicine, Clinical Genetics, Neurology, and Hospital Pharmacy, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands (A.T.P., C.I.C., N.A.B.); the Department of Neurology, University of Pittsburgh, and Neurology Service, Department of Veterans Affairs Medical Center, Pittsburgh (P.R.C., S.A.Z.); Genzyme, Cambridge, MA (D.C., G.J.G., S.L.L., C.M., A.S.); the Department of Neurology–Center for Genetic Medicine, Children's National Medical Center, Washington, DC (D.M.E., R.T.L., J.E.M.); the Department of Neurology, Washington University School of Medicine, St. Louis (J.F., K.N., A.P.); Centre de Référence Pathologie Neuromusculaire Paris-Est, Hôpital Pitié–Salpêtrière, Assistance Publique–Hôpitaux de Paris, Paris (S.H., P.L.); the Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, NC (P.S.K.); the Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York (D.J.L., M.W.); and Tower Hematology Oncology, Beverly Hills, CA (D.J.P., B.R.).

Address reprint requests to Dr. van der Ploeg at the Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Dr. Molewaterplein 60, 3015 GJ Rotterdam, the Netherlands, or at a.vanderploeg@erasmusmc.nl.

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NEJM -- A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease