Enzyme Therapy in Type 1 Gaucher Disease: Comparative Efficacy of Mannose-Terminated Glucocerebrosidase from Natural and Recombinant Sources

  1. Gregory A. Grabowski, MD;
  2. Norman W. Barton, MD, PhD;
  3. Gregory Pastores, MD;
  4. James M. Dambrosia, PhD;
  5. Tapas K. Banerjee, MD;
  6. Mary Ann McKee, MD;
  7. Colette Parker, MD;
  8. Raphael Schiffmann, MD;
  9. Suvimol C. Hill, MD; and
  10. Roscoe O. Brady, MD
  1. From Children's Hospital Medical Center, Cincinnati, Ohio; Mt. Sinai School of Medicine, New York, New York; and the National Institute of Neurological Disorders and Strokes, Bethesda, Maryland. Requests for Reprints: Gregory A. Grabowski, MD, Children's Hospital Medical Center, Division of Human Genetics, Pavilion 3-52, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. Grant Support: A grant to Dr. Grabowski supported only and in toto the patient-related study costs. Other grant support was provided by the General Clinical Research Center at Mt. Sinai Medical Center (grant 2 M01 00071) and the Markey Center for Pediatric Molecular Genetics at the Children's Hospital Medical Center, Cincinnati, Ohio.

    Abstract

    Objective: To compare the efficacy of mannose-terminated glucocerebrosidase prepared from natural (alglucerase; Ceredase, Genzyme Corp., Cambridge, Massachusetts) and recombinant (imiglucerase; Cere-zyme, Genzyme Corp.) sources in treating type 1 Gaucher disease.

    Design: Double-blind, randomized, parallel trial.

    Setting: University medical center and clinical research hospital.

    Patients: 15 patients (4 children and 11 adults) randomly assigned to receive Ceredase and 15 patients (3 children and 12 adults) assigned to receive Cerezyme.

    Intervention: Ceredase and Cerezyme were infused every 2 weeks for 9 months at a dose of 60 U/kg body weight.

    Outcome Measures: Hemoglobin levels, platelet counts, and serum acid phosphatase and angiotensin-converting enzyme activities were monitored every 2 weeks during the trial. Hepatic and splenic volumes were assessed at the time of randomization and after 6 and 9 months of enzyme infusion. Formation of IgG antibodies to Ceredase or Cerezyme was monitored every 3 months by radioimmunoprecipitation assay.

    Results: No significant differences were found in the rate or extent of improvement in hemoglobin levels, platelet counts, serum acid phosphatase or angiotensin-converting enzyme activities, or hepatic or splenic volumes between either treatment group. The incidence of IgG antibody formation was greater in the Ceredase group (40%) than in the Cerezyme group (20%). No major immunologic adverse events occurred in either group.

    Conclusions: Our study shows the therapeutic similarity of Ceredase and Cerezyme. Cerezyme has the advantage of being theoretically unlimited in supply and free of potential pathogenic contaminants.

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    1. Ann Intern Med January 1, 1995 vol. 122 no. 1 33-39
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