Genzyme General and Pharming Report Publication of Study Results for Pompe Disease Therapy

The open-label trial, conducted at Duke University Medical Center, includes three infants with Pompe disease, a rare genetic disorder caused by the lack of the enzyme alpha-Glucosidase, which is responsible for breaking down glycogen into glucose. Patients with Pompe disease experience severe organ and tissue degradation resulting from the accumulation of glycogen in their heart and skeletal muscles.

Patients in the study have been receiving intravenous infusions of recombinant human alpha-Glucosidase purified from CHO cells for over 18 months. Because infants with Pompe disease generally die of cardiac failure before reaching 12 months of age, one of the study’s primary end points was heart-failure-free survival at 1 year of age. Given the limited life-expectancy of infants with this disease, no placebo control was employed. All three infants passed the critical age of 1 year. All currently remain on therapy and have reached the ages of 20 months, 22 months, and 26 months. (Pompe disease also manifests itself in late-onset forms, and can also be fatal for those who develop symptoms as juveniles.)

Trial results indicate that the enzyme replacement therapy may be able to reduce heart size and improve cardiac function. Left ventricular mass measurements decreased during therapy for the two patients who began the trial with increased left ventricular mass and severe cardiomyopathy. Both patients had left ventricular masses reduced to between 60-70 percent of baseline pre-treatment levels. These decreases suggest an overall reduction in heart size, a finding that was confirmed with chest X-ray images. Improved cardiac function has been sustained in all three patients in the trial.

Improvements in skeletal muscle function were also observed, although the significance and extent of these improvements have been more variable than with those in cardiac function. One patient showed marked improvement and currently has normal muscle tone and strength, as well as normal neurological and motor development evaluations. Muscle biopsies confirmed that significant reductions in glycogen accumulation occurred in one patient after enzyme replacement therapy. Initial improvements in two patients declined coincidental with a rise in antibody titers.

Study results indicated that recombinant human alpha-Glucosidase was generally well tolerated. Two patients experienced mild infusion reactions consisting of fever and rash. These reactions have been easily managed with routine pre-treatment medication. All hematological, liver and renal function parameters have remained in the normal range throughout the therapy period for all patients.

“Based on the encouraging results of this trial, we will begin very shortly a Phase 2-3 clinical trial for infants with Pompe disease,” said Henri A. Termeer, chairman and chief executive officer of Genzyme Corp. “We hope to subsequently expand this trial to include patients with later-onset forms of the disease. We are optimistic that this next study will demonstrate in a broader group of patients the positive impact of enzyme replacement therapy on Pompe disease.”

Genzyme and Pharming have been working in partnership to develop a treatment for Pompe disease since 1998. George J.M. Hersbach, president and chief executive officer of Pharming, adds: “Today’s clinical results publication is a welcome and exciting confirmation of the earlier published results in the Lancet of July 2000 on our jointly sponsored clinical studies of transgenic human alpha-Glucosidase at the Sophia Children’s Hospital in Rotterdam, The Netherlands, and similar studies at the University Hospital of Essen, Germany.” ……