Transkaryotic Therapies Inc. lost 23.5 percent of its stock value after announcing its decision to abandon efforts to win U.S. approval of Replagal, an enzyme replacement therapy for Fabry's disease.
While Replagal (agalsidase alfa) has made it to market in 27 countries, primarily in the European Union, Transkaryotic Therapies - or TKT - hasn't been able to convince the FDA to give it the go ahead.
On withdrawing its biologics license application, TKT's stock (NASDAQ:TKTX) fell $4.01 Tuesday to close at $13.04.
Michael Astrue, TKT's president and CEO, told BioWorld Today The Street's response was a bit of an overreaction. "I think we have always said on Replagal in the U.S. that we probably would not go ahead, but we were going to give it one more shot, and I think most of the world processed that," he said.
The FDA last year rejected TKT's application to market Replagal as an orphan drug for Fabry's disease, a rare genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Around the same time, the agency gave Genzyme General clearance to market Fabrazyme, also an enzyme replacement therapy, for Fabry's disease. Both companies are located in Cambridge, Mass. (See BioWorld Today, Jan. 14, 2003; Jan. 15, 2003; and April 25, 2003.)
Since Fabrazyme was approved first, Genzyme won orphan status, or the highly coveted seven years of market exclusivity. TKT subsequently could have received FDA approval for Replagal if it could prove that its candidate worked better than Genzyme's.
To do this, the FDA asked TKT to conduct a head-to-head trial comparing Replagal to Fabrazyme.
Astrue said the FDA's request was a surprise.
"We had previously said a head-to-head trial would be impossible to accrue and would be incredibly expensive even if you could accrue it," he said. "So when they came back with that ruling, it was pretty clear that we had no choice but to shut it down."
The trial would be a challenge to enroll because the worldwide disease population is only about 5,000, and for the purposes of another U.S. trial, Astrue said it would be difficult to find na ve patients since most people with Fabry's disease who have been identified are being treated.
Nevertheless, TKT marches on, commercializing Replagal in other parts of the world. Astrue expects approval in Japan and Canada during the second half of 2004.
In recent weeks, TKT and Orphan Australia entered a 15-year marketing and distribution agreement for Replagal in Australia and New Zealand.
A preliminary review of shipments indicates that fourth-quarter sales of Replagal will be flat with third-quarter sales, which totaled about $15.2 million. Although it has not yet released its fourth-quarter earnings, TKT estimates that its cash balance for Dec. 31 will exceed its 2003 guidance of $150 million to $170 million.