Transkaryotic Therapies, Inc., a biopharmaceutical company, announced that it would cease efforts to seek the approval of Replagal (agalsidase alfa) enzyme replacement therapy for Fabry disease from the US Food and Drug Administration (FDA). TKT will continue to market and sell Replagal in countries where it is approved outside the United States, will continue its efforts to introduce Replagal in new markets in 2004, and will continue to supply Replagal to US patients in its ongoing clinical trials.

TKT submitted a request for a Special Protocol Assessment to the FDA in November 2003 to identify a regulatory approach that could lead to US approval of Replagal, where orphan drug exclusivity excludes it from the US market. In its response, the FDA indicated it would expect TKT to conduct a head-to-head trial comparing Replagal to Fabrazyme in patients with Fabry disease as the way to demonstrate either superior safety or efficacy.

"We always characterized this initiative as one that faced significant challenges and one that was not a necessary part of our business plan. We are nonetheless disappointed that US patients will not have the benefits of Replagal," said Michael Astrue, president and CEO of TKT. "Given the limited availability of Fabry patients for clinical trials and the large number of patients necessary to conduct a meaningful head-to- head trial, we feel we should put our resources into expanding the existing Replagal franchise and other important programmes for desperately ill patients."

Replagal is a fully human alpha-galactosidase A protein, produced by genetic engineering technology, intended for long-term treatment of Fabry disease. It replaces the deficient alpha-galactosidase A with active enzyme to halt or reverse the disease process. Replagal has been approved for commercial use in 27 countries, primarily in the European Union.

Fabry disease is a rare, inherited genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. It affects 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. An estimated 5000 patients worldwide are affected by Fabry disease. Due to its rarity and vast array of symptoms diagnosis is often difficult and affected men and woman have a significantly reduced quality of life and a greatly shortened life expectancy.