Pompe Program Update March 2005

Pompe Program Update March 2005

Continued progress is being made in the Pompe program at Genzyme, with the goal of obtaining worldwide regulatory approval for the investigational rhGAA enzyme. There are now over 110 patients receiving investigational rhGAA, and as a result, there are increasing numbers of physicians and hospitals around the world having direct experience with the investigational enzyme.

The submission (MAA) to the European regulatory authorities (EMEA) was formally accepted in December 2004. The regulatory submission to the FDA in the US (BLA) is still on track for mid-2005, with additional international filings to follow. Consultations with regulatory authorities are ongoing, in regards to these submissions and the upcoming Late-Onset Treatment Study. We hope and expect that much progress will be made in 2005.

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 part of the world-wide regulatory filings. While the data from these studies are not yet available, it is anticipated that the clinical investigators will submit the results for publication in 2005.

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 childs 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

The Late-onset Prospective Observational Study (LOPOS) is nearing conclusion, and data from this study are being used in the design of the placebo-controlled Late-Onset Treatment Study (LOTS).

Late-onset treatment studies

As previously announced, additional patients will be recruited for the planned Late-Onset Treatment Study (LOTS). In order to identify potential patients for future Genzyme clinical studies, including LOTS, a " screening study " for those who did not participate in LOPOS has been planned for late-onset patients to begin in the second quarter of 2005 (April-June) in the U.S.

This study is intended to accelerate the enrollment of patients in studies such as (LOTS) by performing some of the screening procedures that are anticipated to be part of future Genzyme studies involving Pompe disease. These procedures will include a skin fibroblast GAA enzyme level assay which can take up to 4-6 weeks to complete.

This study will consist of a single visit to one of the investigational sites. All travel-related expenses for the participant and a companion will be paid for and managed by NORD (National Organization of Rare Diseases), through a grant provided by Genzyme. It is expected that this study will enroll up to 50 patients at up to 5 sites in the United States. We are in the process of finalizing the locations of the participating sites, but expect the initial site locations to include New York, Pittsburgh, and Los Angeles.

Participation in this study is not an eligibility requirement for LOTS and does not guarantee that the participant will be further screened or enrolled in the LOTS study. It is likely, however, that the majority of patients who are enrolled in LOTS will have participated in LOPOS or in this screening study. All patients who are eventually enrolled in the LOTS study must meet all of the established inclusion/exclusion criteria.

At this time, it is anticipated that the LOTS study (Europe and US) will begin in the third quarter of 2005 (July-Sept.). Based on feedback we have received from regulatory authorities, we are still working on the design of this study. Every effort is being made to commence this study as soon as possible and more information about the specific inclusion/exclusion criteria, the timing of the study and the number of patients to be enrolled will be made available also as soon as possible.

Details about the LOTS study will be posted on the NIH website, clinicaltrials.gov once the study is initiated. Genzyme will also contact the physicians of those patients (in the US), who have provided authorization to do so, with further information about both the screening study and LOTS when it is available. If you have questions about this, please contact Genzyme Patient Advocacy at 800-745-4447 x16500.

In addition to the planned LOTS study, Genzyme recently initiated a small clinical trial in pediatric patients with late-onset Pompe disease in Rotterdam, The Netherlands. This study began in February, 2005, and is being performed to provide additional data and treatment experience in late-onset patients.

Late-Onset Expanded Access Program (LO-EAP)

The process of initiating the treatment sites for all the patients approved for the LO-EAP has proved to be extremely time-intensive. At this time we are addressing each specific situation on a case-by-case basis. Late-onset patients in Europe, the US, Australia, and Canada are currently receiving investigational enzyme, and we anticipate that the approved late-onset patients in all regions will begin receiving investigational enzyme soon. Enrollment in this program is currently suspended but is anticipated to re-open in the next few months. At that time a limited amount of investigational enzyme will be allocated to the U.S., Europe, and International countries to support this program. Patients who meet the established inclusion criteria will be considered eligible for this program, and if any material remains within the regional allocation after qualifying patients are treated, some patients who may not completely meet the inclusion/exclusion criteria, but who would still be considered to be " severely affected " , may be considered on an exceptional basis. This change may vary by region based on applicable regulatory guidelines, and is being made to accommodate regional differences in medical practice.

Inquiries fielded by Genzymes Medical Information department will be held until active screening begins. More details about this program will be forthcoming.

French ATU Program

The French government has 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

The Pompe Registry has now enrolled almost 50 patients from around the world. Approximately 14 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. However, 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 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. Participating patient information is maintained as secure and confidential. The Registry allows participating physicians to monitor their patients 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 Disease Registry may contact Genzymes 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.