Letter From Jan van Heek

On Saturday, March 9th, 2002, I will be speaking at the VSN (The Dutch Muscular Dystrophy Association, Vereniging Spierziekten Nederland) Annual Patient Conference in The Netherlands. At the conference I will provide a general overview of Genzyme, focusing on our plans to move forward with the development of ERT (Enzyme Replacement Therapy) for Pompe disease. In an effort to keep you informed I would like to share with you some of the highlights of my presentation.

First, thank you for your patience over the last six months as we have made dramatic and significant advancements in the Pompe development program. Genzyme has fundamentally reorganized the structure, organization and leadership of Genzyme’s global Pompe efforts. Twelve key members from the executive teams of Genzyme and Novazyme (a fully owned subsidiary of Genzyme as of 11/15/01) have formed the PLT (Pompe Leadership Team), chaired by John Crowley. We have engaged the best and the brightest individuals in the PLT to move this program forward as quickly as possible. The PLT sets the strategic direction and is responsible for making operational decisions with respect to all aspects of the Pompe program, including: pre-clinical, manufacturing, clinical, regulatory, and business, along with input from Genzyme’s senior executives.

We truly believe that 2002 will finally mark the year of change for the future of Pompe patients worldwide.

In the past, one of the vexing problems has been limited supply of the protein for ERT. We have made significant improvements in both the quantity and quality of enzyme production over the past months. We have transitioned all enzyme production into Genzyme’s own manufacturing facilities and have much more control over enzyme quality, consistency and quantity. We are confident that our manufacturing process changes will ensure adequate product supply in the future.

We will soon be meeting with the regulatory authorities to discuss specific details of the next clinical studies of our CHO cell line product in different patient groups. The specific numbers of patients and inclusion criteria have not yet been presented to the regulatory authorities and therefore, are not yet finalized. Presently, we plan that this will be a multi-center, international trial, with sites in both Europe and the United States. We will disclose more details about the inclusion criteria, specific timeline and overall design of the trial when we receive approval from the regulatory authorities. We anticipate enrolling patients into the new trials as soon as we conclude our discussions with the regulatory authorities.

Please note that the safety and efficacy of our CHO cell line ERT for Pompe disease has not yet been established in large clinical studies. As part of this aggressive development plan we plan to accumulate a strong package of pre-clinical and clinical evidence to present to the regulatory authorities in the future. In closing, I would like to emphasize that our goal is to have both an approved and reimbursed product available to all patients around the world. To achieve this task we need to work together to generate a greater awareness about the life-threatening affects of Pompe disease.

Many patients ask what they can do to help. My response is to ask you to work within your local areas to generate public interest stories focused on Pompe. The more we can raise awareness and recognition of Pompe disease. There is still much work to be done, but by working together we can ensure that the future for individuals and families affected by Pompe will be bright.

At this time I respectfully ask for your continued patience for several more weeks until our discussions with the regulatory authorities are concluded. At that time we will share with you the approved clinical path forward for 2002. In the meantime please direct any questions you may have to Sara Den Besten, Senior Manager of Patient Advocacy (email: [email protected] – phone: (609) 683 – 4400 x119).


Jan van Heek Executive Vice President, Therapeutics and Genetics Genzyme Corporation

(Released March 5, 2002) Mr. van Heek was unable to attend the VSN Conference on March 9, 2002, as initially planned. Philippe van Holle and Dr. Cabri addressed the group in his absence.

Dear Friends,