Shire plc shocked the rare disease community on March 14 when it announced it had withdrawn its BLA for Replagal agalsidase alfa to treat Fabry's disease less than two weeks before a scheduled FDA advisory committee meeting - and that it had no intention to resubmit a marketing application in the U.S.

This week, Shire is set to close down its treatment IND for Replagal, which has been providing U.S. Fabry's patients with access to the drug since October 2009. The move will culminate a cascade of events set in motion by a regulatory crisis that began with the now infamous manufacturing debacle at Genzyme Corp., which led to urgent efforts by FDA to find a substitute to compensate for the shortage of Genzyme's Fabrazyme agalsidase beta, the only drug approved in the U.S. for Fabry's.

Approval of Shire's BLA would have ensured U.S. patients access to the drug, and a choice of treatments when Fabrazyme supplies come back on line. Patients in the U.S. will not have this option because Shire decided to withdraw the BLA after receiving the advisory committee briefing documents, which the company has said indicated FDA would require additional controlled clinical trial data.

Shire has not disclosed what in the documents specifically led it to reach that conclusion.

But after the BLA was pulled, BioCentury received from an anonymous source an unsolicited package of documents that are labeled as FDA briefing materials prepared for the March 27, 2012, meeting of the Cardiovascular and Renal Drugs Advisory Committee.