Genzyme's Scale-Up Issues for Lumizyme Still Not Resolved

March 13, 2009

Genzyme Corporation (Cambridge, MA) has received a complete response letter from the US Food and Drug Administration regarding its application to market Lumizyme (alglucosidase alfa). In its letter, the agency outlines the remaining items that must addressed before the application can be approved. To gain approval, Genzyme must also resolve issues identified in a warning letter that the company received simultaneous to the complete response letter.

Genzyme Corporation (Cambridge, MA) has received a complete response letter from the US Food and Drug Administration regarding its application to market Lumizyme (alglucosidase alfa). In its letter, the agency outlines the remaining items that must addressed before the application can be approved. To gain approval, Genzyme must also resolve issues identified in a warning letter that the company received simultaneous to the complete response letter.

The enzyme replacement therapy Lumizyme, also marketed as Myozyme, is the only approved treatment for Pompe disease, a rare genetic disorder. It is approved by the FDA at the 160-L pilot production scale, but Genzyme is seeking US approval for product produced at the 2,000-L commercial scale at its facility in Allston Landing, MA. The Allston plant currently manufactures the therapy at the 2,000-L scale for international markets. Genzyme had to submit a new BLA because of differences in the carbohydrate structure when the product was compared to the same product manufactured at 160-L pilot scale.

Under the complete response letter, Genzyme and the FDA must finalize agreement on the design of a post-approval verification study to demonstrate the clinical benefit of Lumizyme, as required under the accelerated approval process. In addition, Genzyme said the company and the agency must finalize the Risk Evaluation and Mitigation Strategy (REMS) for the product. Genzyme and the agency have been working closely and making progress toward these goals but were not able to reach them by the PDUFA date.

Genzyme also now needs to resolve issues identified in a warning letter the company received simultaneous with the complete response letter. The warning letter addresses deficiencies related to observations made during an inspection of Genzyme’s Allston Landing manufacturing facility performed in September and October 2008. These issues relate to aspects of microbiological monitoring and controls, production equipment maintenance and certain process controls. Genzyme initially responded to the FDA on October 31, 2008, with a detailed plan and timeline to address all of the agency’s observations. The company provided a progress update on February 23, 2009, confirming that all corrective actions had either been completed or were on schedule to be completed by the original commitment date of March 31, 2009.

BioMarin Pharmaceutical, Inc. (Novato, CA) said the FDA warning letter issued to Genzyme has no foreseeable impact on the supply of Aldurazyme, co-produced by Genzyme and BioMarin at the Allston Landing facility. The warning letter does not require Genzyme to recall or quarantine product. BioMarin and Genzyme have sufficient quantities of finished product on hand to meet current demand and can fill additional product at a qualified alternate fill–finish supplier. BioMarin is also qualifying a third supplier, which it expects to be approved later this year and has no concerns on maintaining sufficient levels of Aldurazyme inventory. BioMarin does not expect that the situation at the Allston manufacturing facility will have any impact on Aldurazyme sales.