By Karen Pihl-Carey

Staff Writer

Transkaryotic Therapies Inc. submitted a biologics license application (BLA) for its Fabry disease product, Replagal, beating out competitor Genzyme General, which intends to file a BLA for a Fabry disease product later this month.

The two companies are in a foot race for orphan drug status, which will be granted to the first product approved.

"It's a significant deal. This is their [TKT's] first filing for a drug approval," said Thomas Dietz, director of research at Pacific Growth Equities Inc., of San Francisco. "They finished the Phase III last year. They're out of the gate.

"So they're on track now to gain approval, barring any missteps, in the year 2000."

Dietz said the fact that TKT submitted its BLA before Genzyme submitted a BLA for Fabrazyme gives TKT an edge for getting approval first and achieving an orphan drug status for the product. He estimates that Replagal would bring in $30 million in sales in 2001, its first full year on the market, and $70 million in sales in 2002. "We think the drug is probably to them worth between $100 million and $150 million in sales the third year out," Dietz told BioWorld Today.

Genzyme said in May it expects to file a BLA for Fabrazyme in late June. (See BioWorld Today, May 3, 2000, p. 1.)

"The first product approved enjoys a seven-year period of market exclusivity," said Richard Selden, president and CEO of Cambridge, Mass.-based TKT. "Having said that, I think the most important thing about Fabry disease in the end is that we come up with a safe and effective treatment, and the more work in Fabry disease and the other diseases that are out there, the better. There are about 5,000 rare genetic disorders and together they affect 20 million people in the U.S. I think general competition is a good thing in this area."

Replagal (agalsidase alfa) is an enzyme replacement therapy that, if approved, would represent the first treatment option available to patients with Fabry disease. TKT also plans to file for regulatory approval in Europe in the second half of this year.

The U.S. submission is based on clinical data from two independent trials conducted in the UK involving a total of about 50 patients. In a 24-week, randomized, double-blind, placebo-controlled study, all 25 patients who completed the study elected to receive Replagal as part of a one-year maintenance study. In another study, 14 out of 15 patients remain on therapy as part of an ongoing maintenance study. In both studies, patients received either Replagal or a placebo by intravenous infusion every two weeks. Data showed an excellent safety profile and a comprehensive clinical effect for Replagal, Selden said, but specifics will be presented later this year at medical meetings.

In January 1999, TKT entered into a collaboration with Sumitomo Pharmaceuticals Co. Ltd., of Point Richmond, Calif., to commercialize Replagal in Japan and other Asian countries.

TKT plans to market the product on its own in the U.S. "Over the course of the past year, we've been building a commercial infrastructure that we believe will very efficiently commercialize our product," Selden told BioWorld Today.

Fabry disease is an inherited rare genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. It causes accumulations of ceramidetrihexoside, resulting in extreme pain, serious renal and cardiovascular disease, and stroke. The disease is estimated to affect one in 40,000 men worldwide, and death typically occurs around age 40 or 50. Between 1,000 and 2,000 patients in the U.S. have the disease.

"I'm really proud of my colleagues at TKT. The filing of our first BLA is a milestone event," Selden said. "Just as importantly, we look forward to the day when Fabry disease is no more than an inconvenience and patients can lead long and healthy lives."

Aside from Replagal, TKT also may file for FDA approval this year of another late-stage product, gene-activated EPO (GA-EPO), Selden said. GA-EPO has completed Phase III trials in renal failure in dialysis patients and in pre-dialysis patients. It also is being tested in a Phase III trial in oncology.

It is the subject of a lawsuit between TKT, its partner Aventis Pharma AG (formerly Hoechst Marion Roussel), of Frankfurt, Germany, and Amgen Inc., of Thousand Oaks, Calif. A trial now is under way. (See BioWorld Today, April 27, 2000, p. 1; May 16, 2000, p. 1; and May 22, 2000, p. 1.)

TKT's stock (NASDAQ:TKTX) closed Friday at $35, up 1.687.