Genzyme Corp has completed its principal phase 4 study of Fabrazyme (agalsidase beta) and performed a preliminary analysis of the results. Completing this study was one of several requirements specified by the Food and Drug Administration when it approved the product for the treatment of Fabry disease in April 2003, Genzyme said in a release.
Fabry disease is a very rare and potentially fatal hereditary disorder that can lead to renal failure, heart disease and stroke.
Fabrazyme was approved in the United States under the FDA's accelerated approval mechanism, which allows the agency to expedite the approval of treatments for serious or life-threatening disorders.
In January 2001, Genzyme initiated a multinational, multi-centre, double-blind placebo-controlled Phase 4 study of Fabrazyme. The trial enrolled 82 Fabry patients, both male and female, with mild to moderate renal disease. Patients were randomized 2:1 at each trial site to receive Fabrazyme at a dose of 1 mg/kg or a placebo.
The trial's primary endpoint sought to determine whether Fabrazyme would reduce the rate of occurrence of certain clinically significant events that mark the advance of Fabry disease, namely the progression of renal, cardiac, or cerebrovascular disease or death. A substantially lower rate of these events was observed among the patients receiving Fabrazyme compared with the placebo patients. This trend was consistent among renal, cardiac and cerebrovasular events, despite the study's small sample size.
A prospectively defined analysis of study results revealed that, at baseline, a larger proportion of patients receiving Fabrazyme were found to have high proteinuria (protein in the urine), an established predictor of renal and cardiovascular disease and the most important determinant of outcomes in this study.
Genzyme plans to submit a summary study report to the FDA this month. Once the FDA has reviewed the data, Genzyme will meet with the agency to discuss their assessment and review next steps. The company will also submit the study results to regulatory authorities in the European Union and certain other regions to fulfil post-approval commitments. Genzyme expects to file the results for labelling purposes early next year, the company release said.
"Completing this study was a tremendous accomplishment, and we are sincerely grateful to the patients and physicians who participated," said Richard A Moscicki, senior vice president and chief medical officer for Genzyme Corp. He added, "We and many others-including members of the FDA advisory committee that evaluated Fabrazyme and the agency itself-identified the challenges inherent in conducting a placebo-controlled study for a progressive and potentially fatal disease when a treatment was commercially available."
Detailed results of the Phase 4 study of Fabrazyme will be presented at several scientific meetings next month. These include the 5th European Roundtable on Fabry Disease being held in Warsaw, and meetings of the American Society of Human Genetics in Toronto and the American Society for Nephrology in St. Louis, the release added.