October 2005 Pompe Program Update

Pompe Program Update

Regulatory Filings The BLA has been filed with the FDA and was granted a "priority review" status. This means that the FDA is required to provide a formal response within 6 months of the date of the submission. In the case of investigational rhGAA enzyme, the BLA was filed on July 28th, 2005. In the time between when a BLA is filed and the FDA renders a decision, there are typically on-going communications between the sponsor company and the FDA. The FDA may have questions regarding the information contained in the filing to which the sponsor company is obliged to provide satisfactory answers. In Europe, the Marketing Authorisation Application (MAA) filing was accepted by the EMEA in December 2004. We are expecting that they will provide a formal response to this submission in the first half of 2006.

Often for drugs in specialized medical areas, the FDA (US) will conduct a panel review session, during which they assemble an independent panel of experts to hear presentations from the sponsor company with regards to the marketing application of a drug. The panel session also contains time for public comments in which members of the public are provided with a forum to comment on the impacts of the disease and the product under review. These are typically patients, caregivers, healthcare providers, and others with an interest in the disease and the approval of the drug that is being reviewed. The panel then provides an opinion on whether the drug should be approved, which is not binding to the FDA. At this time it is unknown whether the FDA will request a panel review session for the investigational rhGAA enzyme.

The decisions from the FDA and the EMEA are currently pending, but when a formal response is received from the FDA and the EMEA, information will be provided with regard to what this might mean for Pompe patients.

If you have questions you may want to contact the International Pompe Association. They may be able to provide you with additional information or direct you to additional sources of information.

Infantile-Onset Clinical Trials and Expanded Access Program

Genzyme continues to enroll eligible patients in the Infantile-Onset Expanded Access Program. The early identification and diagnosis of the children who have this lethal and rapidly progressive form of Pompe disease is of utmost importance for optimal patient management.

A summary of the inclusion/exclusion criteria for the US Expanded Access Protocol is posted on clinicaltrials.gov. Eligibility is based primarily on age at onset of symptoms during a child's first year of life and a documented GAA deficiency, as well as other criteria. In Europe, and other parts of the world, the regulatory environments are different and therefore, the inclusion/exclusion criteria may vary by region. The most expeditious way to have any questions regarding patient eligibility answered will be for a treating physician to contact Genzyme Medical Information, either in the US or Europe.

Late-Onset Observational Study

The Late-onset Prospective Observational Study (LOPOS) recently concluded, and data from this study have been used in the design of the placebo-controlled Late-Onset Treatment Study (LOTS).

Late-Onset Screening Study

The late-onset screening study is enrolling patients from North America. This study is designed to identify potential patients for future Genzyme clinical studies. It was also expected that it would expedite enrollment in studies such as the Late-Onset Treatment Study (LOTS) by performing some of the screening procedures necessary to confirm a diagnosis of Pompe disease. These tests include a skin fibroblast GAA enzyme activity assay and a GAA gene-mutation analysis. The screening study is enrolling patients at 5 sites in the United States. Participation in this screening study is not a requirement for the Late-Onset Treatment Study (LOTS), and those who wanted to be included, but have not been able to participate, are still eligible to be screened for the LOTS clinical trial.

Late-Onset Treatment Study (LOTS)

This study is now active and enrolling patients in the US and Europe. All current study and contact information is posted on clinicaltrials.gov (search for "Pompe. It is anticipated that this study will enroll approximately 72 patients.

Details about this study and contact information for the investigational sites are available on www.clinicaltrials.gov") and you may also contact the Genzyme Medical Information Department with questions about this study. In addition, patients who participated in the LOPOS study or the screening study may be contacted by one of the sites. Pompe patient organizations have also been notified of the start of this study (i.e. IPA, AMDA, UPF, and MDA).

Pompe patients who wish to participate in this clinical trial should try to schedule a visit to the site that is closest to them. It is our hope that clinical trial sites in New York City, Pittsburgh, Washington DC, St. Louis, Los Angeles, Paris (France) and Utrecht (Netherlands) will obtain their IRB's approval to begin enrolling patients as close together as possible. Given that each site has to go through this process independently, it is typical for some sites to begin enrolling patients sooner than others.

Potential participants are welcome to contact the sites that are currently enrolling, but each site may need to prioritize the scheduling of visits for patients who live in their geographic area. Ultimately the scheduling and enrollment of clinical trial participants is within the discretion of the investigators at the study sites.

Late-Onset Expanded Access Program (LO-EAP)

The Late-Onset Expanded Access Program is now recruiting and enrolling a limited number of patients in all regions. All inquiries regarding this program should be directed to Genzyme Medical Information, through a treating physician. The medical eligibility criteria for the US Expanded Access Protocol are listed on clinicaltrials.gov.

Expanded access programs specific to individual countries The governments of several European countries have authorized the use of investigational rhGAA prior to approval, outside of clinical trials. These are country-specific regulatory mechanisms, such as the ATU program (Autorisation Temporaire d'Utilisation) in France which allow pre-approval access to investigational drugs, for patients suffering from serious or rare diseases. Genzyme is working within the frameworks of these programs, and with the local treating physicians to provide investigational enzyme to patients on a case-by-case in these countries. Genzyme will continue to pursue programs in countries with such mechanisms.

Pompe Disease Registry

The Pompe Registry has enrolled almost 90 patients from around the world. Approximately 40 physicians now actively participate in the Pompe Registry. All Pompe patients who are not receiving investigational enzyme replacement therapy are eligible to participate in the Registry through their treating physicians. Also, participation in the Registry does not preclude patients from qualifying for any future clinical program for which they may be eligible.

The Registry is a voluntary program that is designed to track the natural history of Pompe disease as well as clinical outcomes and disease management. Participating patient information is maintained as secure and confidential. The Registry allows participating physicians to monitor their patient's progress using reports generated by the Registry, and they can compare clinical information from their Pompe patients with the collective data in the Registry. Genzyme continues to encourage physicians to participate and enroll patients in the Pompe Registry.

For more information on the Pompe Disease Registry, visit the website www.pomperegistry.com.

Additional Information Genzyme will continue to provide updated information and keep the patient community informed of developments in the Pompe Program through our Medical Information group and through external communications. We will also continue to work with organizations such as the International Pompe Association (IPA) to ensure that accurate and timely information is available. The IPA and their affiliated organizations, as well as other patient organizations are a primary source of information and support for individuals and families affected by Pompe Disease.

Physicians or patients who would like more information about clinical studies, the Expanded Access Program, or the Pompe Registry may contact Genzyme's Medical Information department.

The email address in the United States is medinfo@genzyme.com and the telephone number is 800-745-4447 or 617-768-9000. In Europe, the email address is eumedinfo@genzyme.com and the telephone number is 31-35-699-1499. Other areas may contact your local Genzyme office, if available, or contact Genzyme Medical Information in the United States.

For more information about Pompe disease from Genzyme, please visit www.pompe.com.