If you've been following Shire Pharmaceuticals and their Replagal saga, you've had quite a few twists and turns to keep you occupied. Replagal (agalsidase) is Shire's alternative to Fabrazyme, the Fabry's disease therapy from Genzyme, and during Genzyme's protracted manufacturing troubles, Shire was only to glad to step up in the market in the US. (Replagal hadn't been approved here, but had been on the market in Europe for some years).

So back in March, it was quite a surprise when the FDA turned down Shire's application. And details of why this happened have been scarce - until now? BioCentury is out with a very interesting story, based on what they say is "an unsolicited package of documents that are labeled as FDA briefing materials" from an anonymous source.

If these are on the level, the FDA seems to have had concerns that Replagal's physical characteristics have changed over the years, due to changes in manufacturing (most specifically, the switch to a bioreactor from roller bottles and the use of a different purification method). The content of sialic acid and mannose-6-phosphate, among other factors, seems to be an issue, and cellular uptake of the final product may have drifted downwards. The FDA seems to have decided that the only way to answer such questions was in the clinic, and that's when Shire seems to have balked.

No one at Shire or the FDA would comment on the authenticity of the documents, as Biocentury says, no one has taken the opportunity to dispute them, either. You wonder just how they walked out of the FDA. . .