Transkaryotic Therapies Inc announced preliminary data from an 80 patient double-blinded, placebo-controlled Phase III study of Replagal (agalsidase alfa), its enzyme replacement therapy for Fabry Disease. Preliminary review of the six-month data did not show a statistically significant difference between treated and placebo patients for the primary endpoint of renal function, as measured by glomerular filtration rate. Additional analyses of these data and data for other endpoints are ongoing.

"Based on our earlier clinical data, we believed that Replagal would demonstrate a statistically significant effect on kidney function after six months of treatment. In hindsight, we believe renal benefits might have been observed more readily over a longer treatment period," said Richard F Selden, President and Chief Executive Officer of TKT. "Although the results of the current clinical study are disappointing, we continue to believe Replagal is saving lives, and we believe that longer term data from these patients will confirm Replagal's efficacy."

TKT also announced receipt of a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) in accordance with the previously disclosed deadline for the FDA's review. As expected, the CRL indicates that the FDA believes the data are inadequate for final approval action at this time, primarily because of continuing questions concerning efficacy, but also indicates that the FDA plans "to discuss the data at the Endocrinologic & Metabolic Drugs FDA Advisory Committee and seek their input regarding its interpretation."

The CRL included a small number of well-defined issues and provided guidance as to the steps TKT should take in order to bolster its case for an accelerated approval based on a histopathological surrogate endpoint. "We believe our data will demonstrate that renal pathology correlates with renal function, and, accordingly, is an appropriate surrogate marker. We look forward to the opportunity to make our case for Replagal in January based on both clinical and surrogate endpoints," Dr. Selden added.

Replagal is approved in 25 countries, but there is currently no approved therapy for this life-threatening disease in the United States. To date, TKT has submitted to the FDA five clinical studies covering Replagal exposures for periods of up to 2.5 years. The Company believes that its FDA submissions demonstrate that Replagal is well-tolerated and has a positive effect in several areas, including kidney pathology and function, cardiac structure and function, and metabolism.

Replagal is a human alpha-galactosidase A protein, produced by genetic engineering technology, intended for long-term treatment of patients with Fabry Disease. It works by replacing the deficient alpha-galactosidase A with active enzyme to stop or reverse the disease process. Patients receive 0.2 mg/kg of Replagal every other week over a 40-minute intravenous infusion and many patients receive Replagal at home rather than in a hospital setting. Replagal is approved for commercial use in 25 countries, including the 15 countries of the European Union. In the United States, Replagal is an investigational product.

Fabry Disease is an inherited rare genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, affecting both males and females, which results in premature mortality in the fourth or fifth decade of life due to kidney disease, heart disease and stroke. In patients with Fabry Disease, globotriaosylceramide (Gb3) accumulates in various organs and tissues of the body due to the deficiency of alpha-galactosidase A. Many cells are damaged by Gb3 including epithelial cells of the kidney, myocardial cells, cells of the autonomic nervous system, and endothelial, perithelial, and smooth muscle cells in the large blood vessels. As a result, the deposits of this material can result in severe kidney damage, cardiovascular disease, stroke, and extreme pain. Due to its rarity and vast array of symptoms, diagnosis is often difficult and affected individuals have a significantly reduced quality of life and a greatly shortened life expectancy. TKT estimates that Fabry Disease affects approximately 5,000 patients worldwide.