Shire Files Marketing Applications for Fabry and Gaucher Disease Drugs

Shire plc (Cambridge, MA) has submitted a biologics license application (BLA) with the FDA for Replagal (agalsidase alfa), its enzyme replacement therapy for Fabry disease. Replagal first received marketing authorization in the European Union in 2001, and is approved for the treatment of Fabry disease in 45 countries.

Replagal is a human form of enzyme alpha-galactosidase A (a-Gal A) manufactured in a human cell line by gene activation. Replagal is the only human-cell-line-derived form of enzyme replacement therapy that is indicated for the long-term treatment of patients with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency).

Replagal is currently available to US Fabry patients under an FDA-approved treatment protocol through which Fabry patients can get early access to the drug during its clinical development. The protocol was set up in response to the ongoing shortage of Genzyme’s Fabrazyme, the only drug currently approved for treatment of Fabry disease in the US. Genzyme faced product shortages when it had to temporarily halt manufacturing at its Allston Landing, MA plant because of contamination in one of its bioreactors. Shire expects its Replagal supply to be adequate to meet anticipated global demand.

Shire also has an FDA-approved treatment protocol to allow early patient access to another drug, velaglucerase alfa, for Gaucher disease, which addresses another Genzyme drug shortage, this one of Cerezyme, a Gaucher treatment.

Shire has submitted marketing applications in the fall of 2009 for velaglucerase alfa in the US, EU, and Canada. In the US, the application is being reviewed by the FDA under priority review with a PDUFA date of February 28, 2010. The European regulatory authority has granted accelerated review for the EU application.The FDA recently completed the pre-approval inspections of Shire's Cambridge and Lexington Massachusetts facilities for the manufacturing and testing of velaglucerase alfa. These inspections were an important milestone in the review and approval process for the US NDA.