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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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June 27, 2012

Shire's Replagal Problems: An Inside Look?

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Posted by Derek

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. . .

Comments (3) + TrackBacks (0) | Category: Regulatory Affairs


1. petros on June 28, 2012 6:10 AM writes...

That issue could explain a lot

Replagal was actually originally filed before Fabryzyme but was initially rejected and the Orphan Exclusivity of the latter then precluded approval for 7 years.

Given the acute shortage of Fabryzyme, due to Genzyme's manufacturing woes, and the fact that Shire has been marketing Replagal outside the US since 2001, it seemed very odd that the FDA laid down such conditions.

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2. davesnyd on June 28, 2012 7:46 AM writes...

So-- was this a triumph or a failure for the FDA?

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3. Steve on December 9, 2012 11:21 PM writes...

Why not approve the drug, which has been available for years in Europe, and require manufacture in the U.S.? Or establish a time bar (milestone) for remedy of the quality control concerns? People die from this disease, and quality of life suffers. Another example of government bureacracy. Disgusting!

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