International Pompe Association

Conference Reports - 2003

October 31 - November 2, 2003
Heidelberg, Germany

Documents available for download:

  • A conference report by Betty Cook, Mieke Donk and Maryze Schoneveld van der Linde, as posted to GSDnet. (PDF, 96.5 kB)
  • The conference proceedings, including a Supplement with the transscript of Tiffany's video presentation. (PDF, 554 kB)

In a Question and Answer session Genzyme answered questions submitted to them by email, as well as those from the patients present.

DVD’s of the Conference are also available. Click here for more information.


The 2003 IPA conference was a huge success. Congratulations to Thomas Schaller, Helmut Erny and their families, for the friendliest, best-organised, content-rich conference I have ever attended. (Tiffany House)

Note: Some questions and answers have been added ( which were not addressed at the session) or explained further. They will clarify the report for those who were not present or not able to listen to the presentation. Question forum: Frank Ollington (PhD, Senior Vice President, Genzyme Therapeutics), Sara Den Besten (Senior Manager, Patient Advocacy), Khazal Paradis (Vice President, Clinical Research & Therapeutics)


Randall House opens the session and introduces Frank Ollington.


Frank Ollington introduces the attending Genzyme people and gives a presentation on manufacturing and stock management.

  • Purpose: sharing the status and planning of the Pompe program, and to have supportive, open dialogue and discussion.
  • Goal: to develop and gain regulatory approval for an enzyme replacement therapy for Pompe disease so as to make the drug available to as many patients as possible.

Summary of the presentation

Genzyme manufacturing process is going well and proceeding successfully. Genzyme has enough drug supply to conduct the development program. We also recognize that there has not been and still is not enough enzyme to satisfy patient needs.

The 160 L production is ongoing. The process validation is almost complete. This information is necessary for a regulatory dossier.

The stock situation is such that there is still limited quantity of drug available to offer for expanded access.

The 2000 L capacity is required for commercial use and additional clinical initiatives. It is expected to be available in late 2004. It is anticipated that it will be included in the 1st regulatory submissions in an effort to make the 2000 L material available with the MAA approvals.


At the IPA meeting in Naarden 2002 Synpac CHO rhGAA was presented as the miracle drug. What happened with Synpac?

Genzyme conducted a comprehensive, blinded pre-clinical analysis comparing all four Pompe enzymes. The analysis showed that Genzyme’s internally developed CHO (Chinese hamster ovary) cell based product, when compared with the Synpac enzyme, provided a similarly robust response profile in terms of glycogen clearance. Due to our prediction that we will be able to produce greater yields of the Genzyme CHO enzyme, we believe this is the most efficient path forward to market approval on both clinical and manufacturing considerations.

What makes you so sure that you can make the improvement of 50%?

There is improved production in the 2000-L bioreactor as compared to smaller bioreactors. There are no guarantees this will continue but Genzyme has good experience manufacturing other enzyme replacement therapies.

As far as supply problems, do you consider the number of patients in the future? How many patients can be supplied out a 2000 ltr. Batch? Do you know how much supply you need for the total population?

Yes, we consider the potential number of people with Pompe and the patient population’s anticipated need for supply given the regulations at the time.

These are difficult questions to answer due a number of factors such as not knowing the precise number of people with Pompe globally, the recommended dose is still unknown, dosing is variable based on patient body weight, and the fact that this investigational enzyme has not been approved. 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.

What is the present consumption and what is the projection for on shelf material in the next 6 months?

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.

Are all the patients being supplied out of the 90 L bioreactor at this point?

No, eventually the clinical trial participants are expected to receive material from the 160 L bioreactor.

Khazal Paradis, MD on the clinical update

Goal: to develop and gain regulatory approval for an enzyme replacement therapy for Pompe disease so as to make the drug available to as many patients as possible.

Late-Onset Pompe Disease Questions

What are your plans for studies for late-onset patient?

Genzyme is pleased to be moving forward with the expansion of our Pompe program, to now include studies in the late-onset population. A prospective observational study in approximately 60 patients with mild to intermediate late-onset Pompe disease is planned to begin at sites in the United States and Europe in early 2004. Although this 12-month study will not involve investigational treatment drug, the data from this study will help design the placebo-controlled clinical trial.

This observational study will provide information on the clinical presentation of late-onset Pompe disease and the variability of the disease over time and between patients. This will be valuable in determining appropriate assessments and clinical outcomes for future studies.

A subset of patients involved in the observational study, who meet the inclusion criteria, are anticipated to be enrolled in a placebo-controlled, dose ranging clinical trial, expected to begin in 2004. Participation in the clinical trial is not guaranteed to all observational study participants nor is participation in the treatment trial required for participation in the observational study.

What are the eligibility criteria to participate in the late-onset observational study?

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 because we need to have participants perform multiple assessments, for example pulmonary and muscle testing, to help us understand disease progression.

If enrolled at a site in the U.S, the study will likely include patients eight-years-old and older while in Europe, patients must be 18-years-old and older.

Please note that the late-onset study protocols have not yet been finalized so the specific (inclusion/exclusion) criteria could change.

Where are the study sites located?

Sites for the Late-onset Observational Study will be in the United States and Europe. Once the Institutional Review Board approves a site, Genzyme will be able to announce the site locations and study investigators. Genzyme plans to also contact the IPA board members at this time.

Can I participate in the Late-onset Observational study, if I do not live in one of the countries where the study sites are located?

While there will be 5 study sites in 3 countries, patients from other locations may still be screened for inclusion in the observational study. As planned, it is a 12 month study with multiple assessments requiring travel. The principal investigator will need to determine that travel to they study sites which the patient is enrolled will not 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 sites country.

All patients will need to verify that either their health insurance will cover them at the study site or that they will pay for their own medical costs (unrelated to the trial).

Do I have to participate in the Late-onset Observational Study to participate in the planned Late-onset Clinical Trial?

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.

What about the dosage?

The appropriate dose is not yet known. Data from current clinical trials, designed to establish efficacy, will be used to establish the appropriate recommended dose. In the future, the Genzyme sponsored Pompe disease registry may also provide additional information about dosing.

On Registry Program- How does Genzyme intend to find physicians? Why not patients with physicians we already know?

Four Pompe experts have helped develop and validate the Pompe Disease Registry. Participation in the registry is open to all people with Pompe through their physician while the timing of initiation will likely vary. The patient organisations and Genzyme will work together to communicate about the Pompe Disease Registry as the program develops. The patient organizations may inform their members who may in return inform their physicians.

We also encourage you to consider participating in Genzyme’s Pompe disease registry. This registry will help improve knowledge about Pompe disease by documenting the natural course of the disease, clinical outcomes and disease management.

Expanded Access Questions

What about the Expanded Access program. Will patients receive treatment in a facility close by? Who will set all of this up?

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 IRB ethics board.

Will you please explain the expanded access program for Pompe?

Yes, Genzyme is pleased to be moving forward with expansion of our program for Pompe, to now include an expanded access program. We are working to ensure that all of the necessary regulatory and medical resources are in place for this program.

The company is creating two expanded access programs, one focused on infantile-onset patients and the other on late-onset patients. The former will open first for severely affected infants who are ineligible to participate in Genzyme’s ongoing clinical studies. The latter is anticipated to include a limited number of patients who likely would be ineligible for the placebo-controlled late-onset clinical trial because of the severity of their disease. Initially, the late-onset program 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.

Genzyme will work with regulatory authorities, government officials, clinicians and patient associations to pursue the appropriate mechanisms for expanding access to rhGAA. Availability and timing of the expanded access program will vary based on geography.

Do I qualify for Expanded Access Program?

Eligibility for the Expanded Access Program for infantile onset Pompe disease and for 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 applicable expanded access protocol in order to qualify to receive investigational enzyme replacement therapy.

The infantile-onset expanded access program is designed for patients who demonstrate onset of symptoms before the first year of life and do not qualify for any clinical trial. The late-onset expanded access program is for patients with severe respiratory involvement requiring continuous ventilatory support and who have severe muscle involvement resulting in non-ambulatory condition.

Your/your child’s physician will work closely with Genzyme to see if you/your child meet the eligibility criteria. In addition, there must be available product, local regulatory authorization, qualified physicians and appropriate medical facilities in place before a patient can receive therapy through the expanded access programs.

How do I enroll/ refer for enrollment in an Expanded Access Program?

For US and international: If you are interested in participating in an Expanded Access Program, you or your physician may contact Genzyme’s Medical Information department. The email address in the United States is and the telephone number is 800-745-4447 (press 2).

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

When will the Expanded Access Program begin?

Genzyme initiated the infantile-onset expanded access program in October. The late-onset expanded access program is anticipated to begin later this year (2003). Although the program may have begun, the timing and availability may differ in each country depending on local regulations.

How many patients can be treated in the Expanded Access Program? You had been saying there would be an Expanded Access Program when there is sufficient supply.

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. However, we currently cannot predict exactly how many patients will be enrolled in the program, due to a number of factors; including a limited supply of enzyme and the fact that dosing for this enzyme is based on a patient’s body weight which will vary from patient to patient.

What happens if more people qualify for expanded access than the product supply can support?

Our goal is to accommodate as many patients as quickly as possible. However, our first priority of the Expanded Access Program is to offer treatment to patients more severely affected by this disease, and who meet the criteria outlined in the protocol. If we receive more requests from patients than we have enzyme, then the patients contact information will be gathered and as supply becomes available, Genzyme will resume screening for the expanded access program.

Patients are under the impression they can receive Expanded Access (compassionate use) immediately. They get frustrated, they think there is a 30 day waiting period.

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 then agree to collect medical information and obtain institutional approvals through their IRB ethics board. The necessary regulatory and institutional approvals must be in place before someone may receive treatment through the expanded access program. This process takes time.

Can late onset patients request expanded access in every country?

Yes, already several requests have reached Genzyme. There are no approvals for severely affected late-onset expanded access yet. It is anticipated near the end of 2003 a limited number of patients may be included into the late-onset expanded access program.

Will the patients in Rotterdam currently in trials, be included, both infantile and late onset as well as those who have not been transitioned yet?

Yes. If the question is, will they be transition to the Genzyme internal CHO product.

What is the date for the submission of data for registration of the drug?

Since the submissions are based on the timing and results of ongoing clinical trials, it is difficult to predict the date for registration. The present estimations are for 2005 in the US and fourth quarter 2004 in Europe. Currently the FDA wants to see data on the 1602 study (infantile patients < 6 months). In Europe, the submission may be based on the 1702 study (infantile patients > 6 months < 36 months). The sooner all patients are enrolled the better. Quality of data will determine the outcome.

What about the expanded access in Australia?

Genzyme will work with regulatory authorities, government officials, clinicians and patient associations to pursue the appropriate mechanisms for expanding access to rhGAA. Availability and timing of the expanded access program will vary based on geography.

On the registry. Do you plan to use the Rotterdam/IPA Questionnaire?

Medical expert from Rotterdam, including Dr. v.d. Ploeg have helped develop and validate the Pompe Disease Registry.

The IPA/ Erasmus University Questionnaire is self-assessed, retrospective patient information, while the Genzyme-sponsored Pompe Disease Registry includes prospective and retrospective medical information reported by physicians.

The Genzyme-sponsored Pompe Disease Registry is a multi-center, observational program that tracks the natural history of patients with Pompe disease and their outcomes with ERT and who have agreed to participate in the Registry. This program allows physicians to directly enter specific medical information (for example, physical exam and muscle assessments) in to the Registry database. This data is updated periodically and can be viewed in aggregate by participating physicians.

Therefore, it is anticipated that the Genzyme Registry program will complement existing datasets captured by the IPA/Erasmus University Questionnaire.


Plans for 2004

  • to provide sufficient supply of enzyme
  • evidence of safety and efficacy
  • obtain approval for the largest number of people


Sara Den Besten on Patient Advocacy

Shared mission, working together. You are your best advocate.

General Session Questions

What can we do about the Questionnaire?

A lot of patients did not see the importance of the questionnaire and also assumed Genzyme would do its own registry. How can we emphasize the importance of the questionnaire for patients themselves and that this information will be utilized. If we can do this more patients will participate.

The IPA/Erasmus University Questionnaire definitely offers important information and is anticipated to be a complement to information collected through clinical trials and the registry. Genzyme is happy to discuss with the IPA board on how we may explain together the value of the questionnaire to the patients.

If physicians need to call in how do we get the word out about Pompe disease?

Patients and patient organizations may play an important role in raising awareness of Pompe disease. Patient organizations have both partnered with Genzyme and initiated independent initiatives to improve understanding of Pompe disease. For instance, the AGSD and the AMDA both published and distributed informational material on Pompe disease. Genzyme has also worked with patient organisations nationwide to educate physicians and insurers.

Allied patient groups such as Eurordis and NORD also have extensive experience that we may learn from in getting the word out about Pompe.

Will you please address the potential price and reimbursement of an enzyme replacement therapy for Pompe given that Genzyme has a number of expensive therapies already approved? Is this an extraordinary expensive drug? And will you get it approved for reimbursement-if it is approved?

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.

With thanks to the panel the discussion is closed.

Pompe Conference Heidelberg 2003 on DVD

We are proud to be able to report that thanks to Mr T Schaller and his team the conference proceedings of the IPA conference 2004 in Heidelberg, Germany, are now available on DVD. You can order this DVD (the proceedings consist of 4 DVD’s in 2 boxes) through the IPA secretariat; the price is € 30. After you transfer the money to the under-mentioned account, the DVD will be sent to you. Please mention on your transfer of money if you need a PAL or NTSC version of the DVDs. (Another method of payment is through the paypal system. For more information, please click here.)

The professionally made DVD’s give you very good inside information about research and the state of the art. For patients it is very interesting to see the video from Tiffany who has received treatment for 5 years now. On the PowerPoint presentation given by Mr Wijnen you can see what happens with a baby and its family participating in the first ERT trial and in the following period.

The information is useful not only to patients but also to the specialists involved in the care of Pompe (AMD) patients.

IPA bank details

Rabobank, the Netherlands
Rabobank Account: International Pompe Association,
Account Number 30 47 66 364

For International transfers you will need the following details

IBAN number NL77 RABO 0304 7663 64 (International Bank Account Number)
BIC code RABO NL 2 U (Bank Identification Code)

You may like to visit if you are not sure which TV system is used in your country.

AGSD (UK)/IPA Conference and IPA AGM

Last but not least we would like to invite all IPA members to the next IPA conferenceand AGM. This conference will be held in Birmingham UK on Sunday October 10th, following on from the AGSD (UK) conference on Saturday October 9th. For more information you can check the AGSD (UK) website: and this IPA site, which is updated regularly by Tiffany House (IPA).

On behalf of the IPA board,
Ria Broekgaarden

International Pompe Association
Lt. Generaal van Heutszlaan 6
tel. 00-31-35-5480475
fax 00-31-35-5480499