IPA Summary of Genzyme Press Release

IPA Summary of Genzyme Press Release

The Genzyme press release about the Pompe program put on GSD net by our IPA board member Allan Muir a week ago will probably raise some questions. With a summary description IPA would like to answer them.

Genzyme informed us about their plans concerning late onset studies, Specialized Access Programs and the Genzyme Pompe Registry.

Late-onset Studies, divided into two parts (1) A short-term, strictly observational study that will enroll approximately 60 patients with mild to intermediate late-onset Pompe disease. Data from this study, which will begin later this year, will be used to design a placebo-controlled clinical trial described below. (2) A placebo-controlled, dose-ranging clinical trial, which will include a subset of patients (approximately 40) from the observational study who meet the clinical trial’s inclusion criteria. This trial is expected to begin in 2004 and to last one year.

Specialized Access Programs Genzyme is creating two programs by which critically ill patients may receive ERT before the drug receives market approval. Initially, enrollment will be limited to a relatively small number of patients because of product supply constraints.

Infantile-onset Expanded Access Program (EAP)

The Infantile-onset Expanded Access Program will broaden patient access to rhGAA (Myozyme) utilizing geographically specific regulatory mechanisms. Where possible, Genzyme will collect important clinical data on EAP patients through a protocol or series of recommended evaluations at specific time points. The program will open first for severely affected infants and will include a small number of patients initially based on the limited drug supply. Enrollment in the program is expected to begin later this year. Availability and timing will vary based on geography.

Late-onset Specialized Access Program (SAP)

The Specialized Access Program will be made available to severely affected late-onset patients who would likely be ineligible for the placebo-controlled clinical trial because of the severity of their disease.The program, which will collect data under a clinical protocol or a series of recommended evaluations at specific time points, will include a limited number of patients and will be conducted in cooperation with health authorities in a number of countries with regulatory structures that allow pre-approval access to investigational products for patients in need. Enrollment in this program is expected to begin later this year for a small number of patients from countries whose regulatory authorities have already been working with Genzyme to approve the program to allow pre-approval access to investigational products for patients in need. It will be expanded to include patients in more countries as more rhGAA becomes available.

Genzyme Pompe Disease Registry

Enrollment in this Pompe disease registry is expected to begin within the next several months. This registry is a database of medical information. The collective information from this registry will be used to increase the understanding of the disease and to monitor patients and their response to treatment over time, with the ultimate goal of improving the clinical outcomes of patients. An individual´s identifiable information in the database will remain confidential. The Pompe Disease Registry is a voluntary program designed to enhance the entire Pompe community’s understanding of this disease, patient outcomes and optimal disease management. Participation is not needed in order to get Myozyme.

Late-onset Studies Questions:

  1. Will I qualify for the late-onset patient clinical trial for Pompe disease that is scheduled to take place in 2004? The late-onset study protocols have not yet been finalized and specific (inclusion/exclusion) criteria have not yet been established. When studies in patients with late-onset disease are initiated, study sites and contact information will be posted at www.clinicaltrials.gov , www.worldpompe.org .

2. Why can’t I participate in a clinical trial?

You and so many others from the Pompe Community may feel frustration during this period of development. Although Genzyme is gaining support from regulatory agencies and has made good progress with manufacturing, they are still restricted by different regulations in various countries and remain limited in the supply of enzyme. They believe that the current and future clinical trial initiatives provide the path forward to obtaining regulatory approvals so that treatment may eventually become available to all people with Pompe disease around the world.

Expanded Access Program Questions:

3. How many patients can be treated in the Expanded Access Program/Specialized Access Program?

Initially, enrollment in the expanded access program will be limited to a relatively small number of patients because of product supply constraints. As product supply grows, Genzyme hopes to gradually increase enrollment over time. Currently Genzyme cannot predict exactly how many patients will be enrolled in the program.

4. When will the Expanded Access Program/Specialized Access Program begin?

It is expected to begin with the enrollment in the Expanded Access Program / Special Access Program in the fourth quarter of this year (2003). Timing may differ in each country depending on local regulations. When the expanded access program is established, the information will be posted on www.clinicaltrials.gov , www.worldpompe.org .

5. When will ERT be available?

Genzyme is dedicated making rhGAA widely available to all patients who need it in the shortest time possible. Genzyme is working closely with FDA and EMEA to ensure that the current and planned clinical studies will provide the necessary data to support approval of treatment with rhGAA in the US and the Europe Union. Approval by them opens a window of opportunity for other continents.

6. Do I qualify for Expanded Access Program/Specialized Access Program?

The specific criteria for eligibility in the EAP/SAP have not yet been finalized.

Although the scope of the Infantile-onset Expanded Access Program (EAP) is not finalized, first priority will be given to severely affected infants who are not eligible for the two infantile onset studies which were initiated earlier in 2003. If a patient meets the criteria for the expanded access program, treatment with rhGAA may be made available to them on a first-eligible, first-treated basis. In addition, there must be local regulatory authorization, qualified physicians and appropriate medical facilities in place before a patient can receive therapy through the EAP. Timing and availability may differ in each country depending upon local regulations.

Although the scope of the Special Access Program (SAP) is not finalized, this program is intended for severely affected late-onset patients who would likely be ineligible for the placebo-controlled clinical trial because of the severity of their disease. The program may include a limited number of patients and will be conducted in cooperation with health authorities in a number of countries with regulatory structures that facilitate pre-approval access to investigational products for patients in need. Enrollment is expected to begin later this year for a small number of patients from countries whose regulatory authorities have already been working with Genzyme to approve the program. It will be expanded to include patients in more countries as material becomes available.

7. Do I have to pay to participate in the program?

Will my insurance cover the cost of the program? Do I need insurance to participate in the program? Genzyme will supply the rhGAA free of charge for the period in which patients are being treated under the the expanded access program. Any other health care related costs are the responsibility of the patient. If your health authority has established a mechanism to allow pre-approval access to reimbursement for investigational products like rhGAA, Genzyme will work with your health authority to help obtain reimbursement for the rhGAA.

8. How do I enroll/ refer for enrollment in the EAP/SAP?

For Patients/ designees: When the Expanded Access Program/Specialized Access Program is established, information will be posted on www.clinicaltrials.gov ., www.worldpompe.org . US/International: If you are interested in participating in the Expanded Access Program/Specialized Access Program, you 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 (press 2). Your physician may also contact Genzyme’s Medical Information department to learn more about the Expanded Access Program/Specialized Access Program. Genzyme will then send you an information release form that must be completed, signed and returned. This completed form allows Genzyme to discuss your potential enrollment in the program with your physician once it is established. Following Genzyme’s receipt of the information release form, the next step is for your physician to contact Genzyme in order for you to be considered for the EAP, as your physician has access to your relevant medical information that is needed to determine eligibility.

EU: If you are interested in participating in the Expanded Access Program/Specialized Access Program, please ask your physician to contact Genzyme’s Medical Information department to learn more about the Expanded Access Program/Specialized Access Program. In Europe, the email address is eumedinfo@genzyme.com and the telephone number is 31-35-699-1499, or contact your local Genzyme office.

Please note, neither your physicians contact with Genzyme nor participating in the Pompe Disease Registry guarantees receipt of enzyme replacement therapy through an expanded access program.

9. What is the difference between a Compassionate Use Program and what I hear being described as an Expanded Access Program?

What is expanded access / compassionate use?

Both are general terms used to describe efforts to provide access to investigational drugs outside of clinical trials during the development process. According to the FDA, Expanded Access is designed to make promising investigational therapies available, outside the clinical trial setting and before approval, to people with serious or life-threatening illnesses, without other treatment options. The expanded access mechanisms provide additional information on the safety and efficacy of the drug without compromising the patient's safety. Although the primary objective is patient treatment, the FDA encourages drug sponsors collect meaningful safety and effectiveness data to further knowledge about the drug’s effects.

10. Manufacturing: Why is there still a limited supply of enzyme?

Genzyme is working hard, and investing significant resources, to increase the supply of rhGAA and to manufacture larger quantities of enzyme. Increase is necessary to meet the priority of Genzyme in order to continue the treatment of patients who are currently receiving rhGAA, to conduct ongoing and planned clinical studies. At the moment rhGAA is being produced on a smaller scale, but Genzyme is simultaneously developing the process to produce the enzyme in larger-scale bioreactors at its primary enzyme manufacturing facility in Allston, Massachusetts, USA. This effort is progressing, and the company expects to begin producing rhGAA at the Allston facility in 2004.

11. How is rhGAA made?

RhGAA is a recombinant human enzyme and manufacturing it is a highly complex, resource-intensive and time-consuming endeavor. The process involves cultivating millions of living mammalian cells under carefully controlled conditions within sophisticated vessels called bioreactors. These cells are engineered to produce high levels of the desired human enzyme. Over the course of several months of cell culture, the enzyme is harvested from the bioreactor and highly purified, tested for quality, and ultimately prepared for administration to patients. When companies first begin manufacturing these enzymes, they necessarily have to first develop the process at a small scale, within a small bioreactor, in order to refine and optimize it, before moving on to a larger scale. This process takes a substantial amount of time, analysis, and resources.

12. Is Genzyme conducting a study of enzyme replacement in siblings with Pompe disease?

A clinical trial is currently being conducted on two siblings with Pompe disease. The protocol defines siblings with identical genetic mutations and different clinical presentation. The study will help address several important questions about variability of response to therapy. The trial is no longer accepting patients.

13. Where can I find more about the results of the first transgene trials and what it is to participate in a trial?

You can find more information on the website of the Pompe center in Rotterdam, the Netherlands, www.pompe.center.nl and on the IPA website www.worldpompe.org . www.ecri.org/documents (Patients Reference Guide: Should I enter a Clinical Trial?)