Fabry Study Demonstrates Sustained, Long-Term Renal Stabilization After 54 Months
- Category: Proteins and Peptides
- Published on Friday, 15 June 2007 04:00
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TORONTO, Canada | June 14, 2007 | Results of a significant Fabry disease study were published in the most recent edition of the Journal of the American Society of Nephrology (JASN)(i). The 54-month phase III, open-label extension study in Fabry disease demonstrated that early intervention with (pr)Fabrazyme(R) (agalsidase beta) preserves renal function and stabilizes renal disease progression in patients with this rare, genetic disease(ii).
"The publication of this study marks an important milestone for Fabry disease," said Dr. Michael West, Head of the Division of Nephrology at the QE II Hospital in Halifax, Nova Scotia, and Fabry disease expert. "Like many treatments for rare diseases, long term data has been limited until this point, due to the nature of the disease and the innovative class of the therapy. This study clearly demonstrates the benefits of treatment earlier in the course of the disease. In contrast patients who are treated too late are more likely to progress to end-stage renal disease."
Fabry disease is a life-threatening, progressive inherited metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-GAL A), which naturally clears the body of harmful fatty substances - primarily globotriaoslyceramide (GL-3). Over time, GL-3 will accumulate to such a degree that it compromises the cells of various tissues, including the kidneys, heart, skin, brain, eventually leading to organ failure. Fabry patients must often cope with significant pain and disability and typically have shortened life spans, with the average life expectancy in the mid forties.
The phase III extension study was undertaken to investigate the long-term safety and efficacy of Fabrazyme. Full approval was received from Health Canada for Fabrazyme 5mg and 35mg vial in 2004. Fabrazyme is an enzyme replacement therapy which substitutes the missing or malfunctioning enzyme in Fabry patients. Administered by an intravenous infusion of a recombinant human form of alpha-GAL, Fabrazyme initiates the breakdown of GL-3 accumulation in the cells allowing the body to rid itself of this excess buildup of harmful fatty substances through the blood stream. Results of the initial 42 months of the phase III extension study are already incorporated into the product monograph.
"The Phase III extension study demonstrates the benefits of long-term use of Fabrazyme through sustained clearance of GL-3 and by limiting the progression of renal disease," continued Dr. West. "Additionally, Fabrazyme is essential for the long-term health of the renal system in these patients."
All 58 patients from the original randomized, double-blind, 20-week placebo controlled trial entered an open-label extension trial in which they received biweekly 1.0 mg/kg infusions of Fabrazyme for up to an additional 54 months.
The study demonstrated that when administered at 1 mg/kg every other week over the long-term, Fabrazyme stabilizes renal disease in patients with Fabry disease. By month 54, all patients who underwent optional kidney biopsies (n=8) maintained complete GL-3 clearance in renal capillary endothelial cells and multiple cell types. Complete clearance of skin (31 of 36 patients tested) and heart (six of eight patients tested) capillary endothelium was also demonstrated.
Six patients demonstrated renal disease progression during the course of the study (between 36 and 54 months of treatment). These patients had common clinical characteristics (age greater than 40 years, significant baseline proteinuria greater than 2g/24hr, and greater than 50% glomerular sclerosis at pre-treatment) which are important risk factors for disease progression. This demonstrates the importance of initiating early treatment with Fabrazyme.
Another key finding is that long-term treatment also improves quality of life and pain for patients with Fabry disease. Pain scores, as measured by the McGill Pain Questionnaire, improved over time for those who reported pain at pre-treatment. Among these patients, statistically significant improvements in mean visual analog score were observed (p= 0.007) at month 54.
Adverse events were generally mild and unrelated to treatment. The most common treatment-related adverse events were infusion-associated reactions, which decreased over time.
Genzyme Corporation is a biotechnology and health care products company that develops innovative products and services for major unmet medical needs. Genzyme Canada Inc., located in Mississauga, Ontario, is the Canadian affiliate of Genzyme Corp., headquartered in Cambridge, Massachusetts.
In addition to Fabrazyme, Genzyme markets several other products for rare diseases. These include (pr)Cerezyme(R) (imiglucerase) for the treatment of Type 1 and Type 3 Gaucher disease and (pr)Aldurazyme(R) (laronidase) for the treatment of MPS I, and (pr)Myozyme(R) for the treatment of Pompe disease.
In 2000, Genzyme Corporation established The Fabry Registry for the medical community to understand the disease and monitor its safety and efficacy for patients.
(i) Germain D., Waldex S., et al. Sustained, Long-term Renal Stabilization After 54 Months of Agalsidase Beta Therapy in Patients with Fabry Disease. J Am Soc. Neph 18. 2007