AMDA
Newsletter Letter to Patients A M D A January 2004 Dear Friends of the AMDA, The beginning of 2004 finds us with hope and anticipation over the possibility of enzyme replacement therapy becoming a reality and also with anguish and despair over the loss of loved ones and the further degradation of our bodies from this horrible disease. Although the availability of enzyme replacement therapy for all Pompe Disease patients is still a dream, significant progress was made in 2003, and it is our hope that this momentum will continue throughout 2004 and in the years to come. As 2004 gets under way it’s important that patients be informed of three significant initiatives that Genzyme is planning to implement throughout the year:
This letter is intended to inform you of these events and to provide you with further information. In addition, the AMDA itself also intends to undergo a bit of a change in 2004. We will attempt to develop several new programs, reach out to new members within the patient community and to focus on those efforts that are truly critical for the patient community. One of the newest programs that has been developed is the Pompe’s Communication Program (see attachment) where the Pompe community is invited to participate in regularly occurring teleconferences. It is very important that Pompe patients have one voice so that they can, among other things, stand strong during the development process of the enzyme replacement therapy (ERT). Everyone wants ERT and Genzyme Corporation is working towards that end, but we must not forget that Genzyme is in business to earn money, and that sometimes clashes with the interests of the patients. A good strong organization, like the AMDA, is therefore necessary to protect the rights of the patients. We need to work together to promote our common interests. The following information packets contain “Frequently Asked Questions” that were presented to and answered by representatives of Genzyme Corporation at the 2003 IPA Conference held in Germany. (http://home.arcor.de/fobrokel/pompe2003) Information
has since been updated (where applicable)
and is current. Late-Onset Studies Genzyme plans to conduct a two-part study of late-onset patients. First, a short-term, strictly observational study, which will enroll approximately 60 patients with mild to intermediate late-onset Pompe disease, will be completed. The study will start in early 2004, and the data collected from this study will be used to help design a placebo-controlled clinical trial. The placebo-controlled, dose-ranging clinical trial will include a subset of patients from the observational study who meet the trial’s inclusion criteria. This part of the study is expected to start late 2004 and to last one year. The late-onset study protocols (observational study and placebo-controlled clinical trial) have not yet been finalized and the specific inclusion and exclusion criteria have not yet been established. The late-onset observational study is expected to include patients with mild to intermediate late-onset Pompe disease. For the purposes of this study, mild to intermediate late-onset Pompe disease is defined as people who are able to walk (may be with assistive device) and who do not require ventilator support while awake. One reason for the specific criteria is the importance of having several testable muscle groups since the investigators need to have participants perform multiple assessments (i.e. pulmonary and muscle testing), to help understand disease progression. If enrolled at a site in the U.S. the study will likely include patients 8 years old and older while in Europe, patients must be 18 years old and older. Consideration for Inclusion into the Late-Onset Study: Independent clinical investigators are responsible for conducting clinical trials and for screening all potential participants. Clinical trial participants will be enrolled only by a clinical investigator after successful completion of the screening process. Although Genzyme does not determine who participates in the clinical trials, with your permission, Genzyme can keep your information and your physician’s contact information. When enrollment for the study begins, Genzyme will forward your information to the investigators conducting the trial. The investigator will contact your physician to discuss the steps necessary to submit your information for screening. Once a clinical trial site has received Institutional Review Board (IRB) approval and enrollment is open, your physician should contact the clinical trial sites directly to inquire about the study and initiate the screening process. Frequently Asked Questions: Question: Where are the study sites located? Answer: Sites for the late-onset observational study will be in the United States and Europe. Once the IRB approves a site, Genzyme will be able to announce the specific site locations and study investigators. Question: May I participate in the Late-onset Observational study if I don’t live in one of the countries where the study sites are located? Answer: There will be five study sites in 3 different countries. Patients from other locations may still be screened for inclusion into the observational study. As planned, it is a 12 month study with multiple assessments requiring patients to travel to the study site. The principal investigator will need to determine if travel to the study site will compromise the health and safety of the patient or the outcome of the study. Genzyme will reimburse patients for travel within the North American continent but any travel or relocation over greater distances will be at the expense of the patient. At the European sites, the primary focus will be to screen patients within the country where the study site has been established. Genzyme will cover the cost of all study related expenses, however, patients will need to verify that either their health insurance will cover them at the study site or that they are able to pay for non-study related expenses. Question: Do I have to participate in the late-onset observational study to participate in the planned late-onset clinical trial? Answer: Yes, the placebo-controlled, dose-ranging clinical trial will include a subset of patients from the observational study who meet the clinical trial’s inclusion criteria. Participation in the clinical trial is not guaranteed to all observational study participants nor is participation in the treatment trial required (only 40 out of the 60 will go onto participate in the late-onset clinical trial). Question: What about the dosage of Myozyme? Answer: The appropriate dose is not yet known, however, the dose range will be between 20 mg/kg to 40 mg/kg in the late onset clinical trial. Data from the on-going clinical trials designed to establish efficacy, will also be used to establish the appropriate recommended dose. In the future, the Genzyme sponsored Pompe Disease Registry may also provide additional information about dosing. Information Required by Genzyme: In the United States to participate in the Late-onset Observational Study, Genzyme requires the completion of several forms:
Additional
information on the Late-Onset Programs (not yet
available) EXPANDED ACCESS PROGRAMS Genzyme intends to provide broader access to Myozyme to severely ill patients who are ineligible to participate in clinical trials by creating two Expanded Access Programs (EAP). The first EAP is focused on infantile-onset patients and the other on late-onset patients.
Frequently Asked Questions: Question: How many patients can be treated in the Expanded Access Programs? Answer: Genzyme’s goal is to accommodate as many patients as quickly as possible. However, the first priority of the EAPs is to offer treatment to patients more severely affected by this disease, and who meet the criteria outlined in the protocol. In addition, there must be local regulatory authorization, qualified physicians and appropriate medical facilities in place before a patient can receive therapy through the Expanded Access Program. If Genzyme receives more requests from patients than they have enzyme, then the patients’ contact information will be gathered and as supply becomes available, Genzyme will resume screening for expanded access. Question: Do I have to pay to participate in the Expanded Access Program or will my insurance cover the cost of the program? Do I need insurance to participate in the program? Answer: Genzyme will only supply Myozyme free of charge for the period in which patients are being treated under the EAP. Any other health care related costs are the responsibility of the patient. If your health authority has established a mechanism to allow pre-approved access to reimbursement for investigational products like Myozyme, Genzyme will work with your authority to help obtain this reimbursement. Question: When will the Expanded Access Program begin? Answer: The Infantile-onset EAP was initiated in October 2003. Although the program may have begun, the timing and availability may differ in each country depending on local regulations. The Late-onset EAP is anticipated to begin in early 2004. Question: Will patients receive treatment in a facility close to home? Who will be responsible for setting all of this up? Answer: After patients qualify for the expanded access program, their physician will work with Genzyme to make the necessary preparations and determine their appropriate treating facility. Treating physicians must agree to collect medical information and obtain institutional approvals through their Institutional Review Board (IRB) or Ethics Board. Question: Do I qualify for the EAP? Answer: Eligibility for the EAP for Infantile-onset and Late-onset Pompe disease is based on meeting criteria defined in expanded access protocols. These protocols are designed to include the more severely affected patients who are not eligible to participate in one of Genzyme’s ongoing clinical trials. Patients must meet all eligibility criteria in the EAP protocol in order to qualify to receive Myozyme.
You can
obtain more information on the inclusion and exclusion
criteria for the Infantile-Onset Expanded Access Program
and Late-Onset Expanded Access Program at the Question: Patients are under the impression they can receive EAP immediately and they get frustrated when they are told they have to wait. Answer: After patients qualify for the EAP, their physician will work with Genzyme to make the necessary preparations and determine their appropriate treating facility. Treating physicians must then agree to collect medical information and obtain institutional approvals from their IRBs and Ethics board. The necessary regulatory and institutional approvals must be in place before a patient may receive treatment through the EAP. This process takes time. Question: What about the EAP in other countries? Can late-onset patients request EAP in every country? Answer: Yes, already several requests have reached Genzyme and Genzyme will work with regulatory authorities, government officials, clinicians and patient associations to pursue the appropriate mechanisms for expanded access to Myozyme. Availability and timing of the EAP will vary based on geography. However, the Late-onset EAP is anticipated to begin in the beginning of 2004. Information Required by Genzyme: In the United States to participate in the Late-onset Observational Study, Genzyme requires the completion of several forms:
You can
obtain more information on the inclusion and exclusion
criteria for the Infantile-Onset Expanded Access Program
and Late-Onset Expanded Access Program at the GENZYME
POMPE DISEASE REGISTRY The Pompe Disease Registry is a multi-center, observational program that tracks the natural history and outcomes of patients with Pompe disease. Participation is open to all physicians managing patients with Pompe disease. Patients will undergo standard medical assessments as determined by the their physician. Data collection will focus on cardiac, muscle, and respiratory manifestations, quality of life, and other clinical assessments that are routinely evaluated for patients with Pompe disease. Investigational enzyme replacement therapy will not be administered as part of the Registry The primary objectives of the Registry are:
As a participant in the Pompe Disease Registry, your physician’s contact information will be on file at Genzyme. The physician can then be contacted directly by the Registry or be notified of new clinical program information. Participation in the Pompe Disease Registry does not guarantee receipt of the drug through a clinical study or other protocol. Information required for all patients that reside in the United States: A. Patient Authorization for Release of Health Information:
B. Contact Information Form:
Frequently Asked Questions: Question: Do I have to participate in the Pompe Disease Registry in order to get Myozyme? Answer: No. The Pompe Disease Registry is a voluntary program designed to enhance the entire Pompe community’s understanding of this disease; to enhance patients’ outcome; and to optimize disease management. Question: I have heard Genzyme talking about HIPAA when referring to the Patient Authorization Form. What does HIPAA mean and does this apply to me? Answer: HIPAA applies only to the patient’s that live in the United States. HIPAA’s official name is the Health Insurance Portability and Accountability Act of 1996. The department of Health and Human Services (HHS) is the primary U.S. federal agency responsible for administering HIPAA. The regulations were drafted by the Secretary of the Centers for Medicare and Medicaid Services (CMS). HIPAA is the federal government’s version of health care reform. It is a comprehensive law that not only addresses privacy, security, and uniform standards for electronic transactions but also addresses portability, fraud, and abuse in health care as well as many other issues. The U.S. Congress has enacted HIPAA in part to balance the needs between effective, efficient health care and patient’s right to confidential treatment of their Protected Health Information (PHI). Standards for Privacy of Individually Identifiable Health Information, Final Rule can be accessed at http://www.hhs.gov/ocr/hippa (pp. 82798-82829). Question: What does Protected Health Information (PHI) mean? Answer: PHI is individually identifiable health information that is transmitted and maintained in any medium (including paper records). Any information that may identify an individual and relates to the past, present, or future condition of the individual is protected (for example, a name, address, telephone number, date of birth, or Social Security number). Question: What does HIPAA mean for me? Answer: Because of HIPAA, policies and procedures must be put into practice to ensure that your PHI is kept confidential. Health care providers may not use or disclose an individual’s PHI without consent or authorization. Question: What else should I know? Answer: Due to federal law regarding the confidentiality of individual PHI, Genzyme may request your signed authorization in order to perform various activities that may involve the use of your PHI. The Patient Authorization Form identifies with whom your information will be shared, how it will be shared and the purpose for sharing your information. At your request your PHI will only be shared with other healthcare providers or insurers who are directly involved in your care. You have the right to revoke this authorization at any time.
Additional
information (when available) will be The
IPA/Erasmus Patient Questionnaire In November 2002, the AMDA, in cooperation with the IPA, International Pompe Association and EMC, Erasmus Medical Center (Rotterdam, The Netherlands), sent out an invitation to Pompe patients to participate in a late-onset Pompe disease investigational study. In the US approximately 45% of the patients in the AMDA registry participated in the survey. Although the initial information has been tabulated, data collection is still ongoing. Genzyme is currently collaborating with the IPA and the EMC (Erasmus Medical Center) to obtain the data gathered in this study so that it can be used in conjunction with the information that will be derived from the Genzyme Patient Registry. Information from both sources should compliment each other since the Genzyme Patient Registry is a physician derived database and the IPA/EMC Patient Questionnaire is a patient derived database. Both should play a vital role in gathering information about the clinical manifestations relating to onset and progression of Pompe disease. Therefore, you are again invited to participate in the IPA/EMC Patient Questionnaire. Participation in the study is totally voluntary and will neither enhance nor deter your acceptance into a study, clinical trial, or and early access program. You are not obligated to participate. Patient confidentiality will be maintained through the use of a numbering system. The information derived from this survey will assist both the medical/professional community and Genzyme in gathering information about the clinical condition and the course of the disease as it pertains to the late-onset patient. Frequently Asked Questions: Question: How do the IPA/Erasmus Patient Questionnaire and the Genzyme Patient Registry differ? Answer: The IPA/Erasmus University Questionnaire offers important information and is anticipated to be a supplement to the information collected through clinical trials and the registry. The IPA/EMC Patient Questionnaire is a self-assessed retrospective patient information (reported by patients), while the Genzyme-sponsored Pompe Disease Registry includes prospective and retrospective medical information (reported by patients’ physicians). Both the IPA/Erasmus University Questionnaire and the Pompe Disease Registry will provide useful information that will further the development of a safe and effective therapy for Pompe disease. Medical experts (including experts from Rotterdam) have helped to develop and validate the Genzyme Pompe Disease Registry. If you did not participated in the IPA/Erasmus Patient Questionnaire initially but would still like to, please send the following information to: AMDA We will then forward to you additional information and a consent form. When you return the consent form, we will forward the Patient Questionnaire. Name: _______________________________________ Address: _____________________________________
Additional Information PLANS FOR 2004:
NEED TO KNOW ITEMS:
For More Information in the US contact:
For More Information in Europe:
MARKETING OF MYOZYME Frequently Asked Questions: Question: Given that Genzyme has a number of expensive therapies already approved, what can patients expect as the potential price of enzyme replacement therapy for Pompe disease? Will it be an extraordinarily expensive drug, and if the therapy is approved, will Genzyme get it approved for reimbursement? Answer: The price of our therapies must be considered in the context of the costs and complexities associated with developing and manufacturing innovative products for patients with complex, rare, debilitating, and multi-systemic conditions. Genzyme’s investments in research and in developing and manufacturing treatments - and our investment in research programs that may never result in marketed products - are largely funded by currently marketed products. For example, the research and development efforts for rhGAA are made possible in large part because of revenues generated by Genzyme’s currently marketed products. Genzyme provides a range of support services for patients around the world, focusing first on access to treatment. We have helped thousands of patients obtain reimbursement from insurance companies and government agencies. We have established assistance programs with the goal that all patients who need treatment will receive it, regardless of their insurance status or ability to pay. And we work with non-profit organizations to help create a health care infrastructure to support care, and to provide free drug to patients in countries where reimbursement is not possible. Question: What is the date for the submission of data and filing for registration of the drug? Answer: Since the submission of data is based on the timing and results of the ongoing clinical trials, it is difficult to predict the date of filing for registration. In the US, the FDA wants to see data on the 1602 study (infantile patients less than 6 months). In Europe the European Regulatory Authority will base its approval on data derived from the 1702 study (infantile patients older than 6 months but younger than 36 months). Therefore, the sooner the enrollment in these studies (1602 and 1702) is complete, the better. In addition, the quality of the data that is derived from these studies will determine the outcome of filing for registration. At this time, it is estimated that filing for registration will take place in Europe in 2005 and in the US in 2006. Question: What is the difference between a Compassionate Use Program and an Expanded Access Program? Answer: Both are general terms used to describe efforts to provide access to investigational drugs outside the 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 illness, 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 to collect meaningful safety and effectiveness data to further knowledge about the drug’s effects. Question: Why can’t Genzyme make enough enzyme to supply a large number of patients? Answer: Genzyme is working very hard, and investing significant resources, to increase our supply of rhGAA and to manufacture larger quantities of enzyme. Genzyme is currently producing rhGAA on a smaller scale, while 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. Question: How is rhGAA made? Answer: 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. Question: What is the present consumption and what is the projection for shelf material in the next 6 months? Answer: Currently, there are less than 50 patients receiving enzyme replacement therapy for Pompe disease. Genzyme is working very hard, and investing significant resources, to increase its supply of rhGAA and expand its capacity to manufacture larger quantities of the enzyme. To date, Genzyme believes that it has developed the sustainable capacity to produce enough supply to meet the growing demands of the clinical program and continue to build the manufacturing capacity to meet the needs of the patient population given the regulations at the time. Genzyme has developed a careful set of planning assumptions and continuously monitors the manufacturing and inventory situation so that enough product will be available to treat all appropriate patients if the product is approved. For More Information in the US contact:
For More Information in Europe:
For additional
information search “Pompe” at: www.clinicaltrials.gov |
© AMDA, Acid Maltase Deficiency Association, Inc. 1997
