Genzyme Corporation has received a complete response letter from the FDA regarding its application to market Lumizyme (alglucosidase alfa) for the treatment of Pompe disease. In its letter, the agency outlines the remaining items that need to be addressed before the application can be approved. Lumizyme is produced at the 2000 liter (L) bioreactor scale at Genzyme's Allston Landing facility.

Specifically, 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 and the agency need to 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. Given the substantial progress that Genzyme had made toward addressing the inspection observations, this warning letter was unexpected.

"We have made an enormous effort for more than two years to make this product broadly available in the United States, so we are obviously surprised and disappointed by this further delay," said Genzyme chairman and chief executive officer Henri A Termeer. "We are confident we will be able to resolve all remaining issues with the FDA within three to six months."

Genzyme believes that all the information requested by the agency is readily at hand and that the company will be able to submit this information within approximately one month. Genzyme and the FDA are developing a work plan that will enable the agency to expedite the completion of its review once all information is received. A satisfactory resolution of the FDA's warning letter pertaining to observations at the Allston manufacturing facility is required before the agency will approve Lumizyme. Genzyme is confident that the products produced at the Allston facility continue to meet the highest quality and safety standards.

To ensure that severely affected adults with Pompe disease in the United States have access to treatment, Genzyme created the Myozyme Temporary Access Programme (MTAP) in collaboration with the FDA in May 2007. The company plans to continue providing Lumizyme free of charge to approximately 170 patients on a regular dosing regimen through this programme until approval.

"We began the MTAP program two years ago to provide short-term access to treatment prior to approval," said Termeer. "We have made an extraordinary lifetime commitment to these 170 people living with Pompe disease. We will work with the agency to resolve the outstanding issues as quickly as possible because the only sustainable mechanism for broader access is through the commercial approval of Lumizyme."

Assuming a six-month delay, Genzyme anticipates the impact on 2009 non-GAAP earnings will be approximately $0.12 per share. This reflects both forgone commercial sales margin and the costs of continued administration of the MTAP programme. Genzyme now expects Myozyme revenue of $370 - $380 million in 2009, assuming a six month delay.

Genzyme currently has US approval to sell Myozyme (alglucosidase alfa) for the treatment of Pompe disease. This product has been reserved for infants and children because its smaller 160 L bioreactor production scale limits supply. Myozyme was approved in the United States in April 2006. Since then, the company has been seeking clearance from the FDA to market alglucosidase alfa produced at the 2000 L bioreactor scale, which will be called Lumizyme in the United States. Genzyme submitted a separate BLA for Lumizyme on May 30, 2008. On October 21, 2008, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee affirmed by a 16 to 1 vote that the Late-Onset Treatment Study established the effectiveness of Lumizyme for the treatment of Pompe disease. A majority of the committee members supported Accelerated Approval (Subpart E). While Genzyme's immediate focus is on obtaining U.S. approval of Lumizyme, the company also plans to submit a supplemental BLA filing for 4000 L-scale production to the FDA during the first half of 2009.

Myozyme produced at the 2000 L scale has already been approved for use in all patients with Pompe disease in more than 40 countries. Outside of the United States, the supply of Myozyme was significantly strengthened on February 26, 2009, by the rapid European Commission approval of 4000 L-scale production. Adult patients internationally have resumed regular infusion schedules and new patients outside of the United States are able to initiate therapy.

One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases.