Shire PLC has withdrawn its U.S. application to market an enzyme replacement therapy for Fabry disease, citing an expected FDA demand for controlled clinical trials.
The product, agalsidase alfa (Replagal), would have competed with a similar agent produced by Genzyme, agalsidase beta (Fabrazyme).
"Recent interactions with the FDA have led the company to believe that the agency will require additional controlled trials for approval," Shire said in a statement.
"No concerns over the product's safety profile were raised by the FDA. Shire has concluded that the likely additional studies would cause a significant delay, and an approval of Replagal for U.S. patients would only be possible in the distant future. Shire has therefore decided to withdraw its BLA [biologics license application]."
An FDA advisory committee meeting to review the Replagal application had been scheduled for March 27.
Shire's decision came just as a long-standing shortage of Fabrazyme appeared to be resolved. Genzyme's main manufacturing plant for the product was shut down in 2009 due to problems with contamination. It has recently won approval to begin producing Fabrazyme at a new facility.
At the end of January, Genzyme said it expected to be able to supply all U.S. patients with full doses of Fabrazyme.
Fabry disease is a rare genetic condition in which the gene for the alpha-galactosidase enzyme is defective. The enzyme digests globotriaosylceramide, a byproduct of cellular metabolism that becomes toxic if not cleared from cells. Patients with the disease experience of range of symptoms including pain and dysfunction in the heart, kidneys, and central nervous system.
Shire expressed disappointment in the FDA's apparent insistence on new clinical trials.
"In 2009, and again in 2011, the FDA encouraged Shire to submit an application for the approval of Replagal," the company said. "The information in the application included relevant updates such as manufacturing and open long-term clinical trial data. These discussions led the company to file a BLA last November in anticipation of a quick review process and eventual approval."
During the Fabrazyme shortage, the FDA allowed Shire to supply Replagal to some U.S. patients on an emergency basis. "Over 1,000 patients have switched to Replagal since the beginning of the supply shortage in mid-2009," Shire said, including about 140 who received the drug free of charge through the company's treatment access program.
These patients will presumably now switch back to Fabrazyme.
Replagal is approved in 46 countries worldwide, including the European Union. Shire said that 70% of the global Fabry population uses its product.