Pompe Program Update December 2004


Genzyme is still on track for the Marketing Authorisation Application (MAA) filing in December with the European regulatory authorities, and they will issue a corporate press release once the filing has been formally accepted. This will be a significant milestone, and we hope that this will be the first of many successful filings for regulatory approval of the investigational rhGAA enzyme. Genzyme anticipates that the European Medicines Authority (EMEA) will render a decision within 12-18 months of the filing, but this timeline is highly variable and is subject to change.

Genzyme also anticipates filing a Biologics License Agreement (BLA) with the US Food and Drug Administration (FDA) by the middle of 2005. Additional international filings will follow.

Overall, the last 6 months have been quite extraordinary for the Genzyme Pompe Program. Three clinical trials are fully enrolled, the Expanded Access Program has initiated approximately 40 new infantile and late-onset patients on investigational enzyme therapy, and we will continue to see patients treated and enrolled in this program.

Genzyme Pompe Program Update

Infantile-Onset Clinical Trials and Expanded Access Program Genzyme has two clinical trials for infantile-onset patients that are fully enrolled. The data from these studies will be a critical piece of the world-wide regulatory filings. The data from these studies are not yet available, but once they are, we anticipate the clinical investigators will submit the results for publication.

Genzyme will continue to enroll eligible patients in the Infantile-Onset Expanded Access Program. The inclusion/exclusion criteria for this program are posted on clinicaltrials.gov, and eligibility for this program is based primarily on an onset of symptoms during a child’s first year of life as well as a documented GAA deficiency. The best way to get more information regarding patient eligibility is for a treating physician to contact Genzyme Medical Information, either in the US or Europe.


Late-Onset Observational Study and Clinical Trials

There are some recent developments in the programs for late-onset Pompe patients.

The Late-onset Prospective Observational Study

(LOPOS) is fully enrolled with 58 individuals with “mild to intermediate” late-onset Pompe Disease. The 3-month interim analysis has been completed, and data from this study is being used to design the placebo-controlled Late-Onset Treatment Study (LOTS).

The placebo-controlled clinical trial will include a sub-set of the participants in LOPOS who meet the clinical trials inclusion/exclusion criteria, and will also include additional late-onset patients, who were not enrolled in LOPOS, who also meet the clinical trial’s inclusion/ exclusion criteria. In addition to the existing LOPOS sites, there will also be additional study sites needed, most likely in the United States. The decision to increase the number of patients in this study was made to increase the statistical power of the study. The additional patients will most likely come from North America and Europe. At this time, Genzyme is in the process of finalizing the study design. More information about the specific inclusion/ exclusion criteria, the timing of the study, the number of additional patients, and the location of the study sites will be provided to the International Pompe Association when it becomes available. Details about this study will also be posted on the NIH website, clinicaltrials.gov once the study is initiated. If you have questions about this study, please contact Genzyme Medical Information at 800-745-4447.

Genzyme will contact the physicians of those patients (in the US), who have provided authorization to do so, with further information about eligibility for this study when it is available. Ultimately, the enrollment of study subjects is the responsibility of the Investigators, and Genzyme, as the sponsor company will not have any influence over this process. If you have questions about this, please contact Genzyme Patient Advocacy at 800-745-4447 x16500.

In addition to the planned Late-Onset Treatment Study, Genzyme recently decided to initiate a small clinical trial with 5 mildly affected ambulant patients, 5-18 years of age in Rotterdam, the Netherlands. This 6-month study will begin in the first quarter of 2005, and is being performed to provide additional data and treatment experience in late-onset patients. .

Late-Onset Expanded Access Program

Genzyme is actively involved in the process of initiating the sites for ALL patients currently approved for the Late-Onset Expanded Access Program. Late-Onset patients in Europe and Canada are receiving investigational enzyme, and it is anticipated that the approved late-onset patients, in all regions, will begin receiving investigational enzyme soon.

Genzyme will continue to field inquiries regarding other potentially eligible late-onset patients, but will not be actively screening or enrolling any additional patients for this program, at the present time. All questions about eligibility for the program should be directed, through a treating physician, to Genzyme Medical Information. The primary medical criteria are dependence on a wheelchair and use of invasive ventilation on a continuous basis. Genzyme does not anticipate that they will be able to enroll additional late-onset patients through our Expanded Access Program in the near-term, but will re-evaluate this periodically.

French ATU Program

The French government recently authorized the use of investigational rhGAA for some French patients through their ATU program (Autorisation Temporaire d’Utilisation). This program is the sole regulatory mechanism that the French government uses to make non-approved drugs available to patients, prior to approval outside of clinical trials. Genzyme will also pursue programs in other countries that have similar mechanisms.

Pompe Disease Registry

Genzyme is excited about the progress that has been made with the Pompe Disease Registry. The Registry is a voluntary program that we feel will do much in the way of improving knowledge about Pompe by documenting the course of the disease, clinical outcomes, and disease management.

40 Physicians around the world now participate in the Pompe Registry which has resulted in the enrollment of approximately 20 patients. All Pompe patients who are not receiving enzyme replacement therapy are eligible to participate in the Registry through their treating physicians. However, participation in the Registry does not preclude patients from qualifying for any future clinical program for which they may be eligible.

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. Genzyme 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 Disease Registry may contact Genzyme’s Medical Information department.

The email address in the United States is [email protected] and the telephone number is 800-745-4447 or 617-768-9000. In Europe, the email address is [email protected] 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.