The IPA homepage can be reached at 

http://www.worldpompe.org

Genzyme’s Pompe Program Update
February 2003

Genzyme continues to make good progress within its program to develop a treatment for Pompe disease.  Since our efforts are being followed closely by patients, physicians, health authorities and others, we are pleased to continue to provide regular reports on our progress.  Below we offer an update on the status of key parts of our Pompe program.

Clinical Trials
Genzyme plans to conduct two clinical trials this year of its recombinant human alpha-Glucosidase enzyme (rhGAA).  Both studies will focus on patients with the infantile-onset form of Pompe disease, in which symptoms manifest themselves during the first year of life.  We have received IRB or Ethics Committee approval to begin the first of these trials (study 1702) at five research hospital (Duke University Medical Center, Cincinnati Children's Hospital Medical Center, and the University of Florida at Gainesville in the United States, the Royal Manchester Children's Hospital in the United Kingdom, and Hôpital Universitaire Debrousse in Lyon, France).  Patient screening has begun, and the first patient infusion is expected to occur shortly. We anticipate opening the trial at other sites soon.  This study will include up to 16 children between the ages of six months and three years.  Detailed information about the trial's entry criteria and protocol can be found at:

www.clinicaltrials.gov.

The second trail 9study 1602) is scheduled to begin in the spring, and will include up to 16 infants younger than six months of age at the time of their first infusion.  We expect to complete enrollment in both studies this year.  We plan to begin clinical trials for patients with the late-onset form of Pompe disease once a sufficient supply of the rhGAA is available.

Manufacturing
Genzyme is working as fast as possible, and investing significant resources to increase its supply of rhGAA and expand its capacity to manufacture larger quantities of the enzyme.  This process began last year, when we shifted the focus of our development program to this product after concentrating previously on two first generation enzymes.  To date, Genzyme has developed the sustainable capacity to produce enough rhGAA to conduct the two announced infantile-onset clinical studies and to support patients who took part in clinical studies of the first-generation enzymes. 

Manufacturing recombinant enzymes 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.  Theses cells are engineered to produce high levels of the desired human enzymes.  After 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 such as Genzyme 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 "scaling-up" process takes a substantial amount of time, analysis, and resources. 

Genzyme is currently producing rhGAA on this smaller scale at its development and pilot manufacturing facilities, while simultaneously developing the process to produce the enzyme in large-scale bioreactors at its primary enzyme manufacturing facility in Boston.  This effort is progressing well, and we expect to begin producing rhGAA at the Boston facility early in 2004. 

Expanded Access/Compassionate Use
Sufficient quantities of rhGAA are available to conduct the two planned infantile-onset clinical studies and to support patients from earlier clinical studies of first-generation enzymes.  Until adequate product inventory exists, priority will and must be given to continue supplying enzyme to these patients and to the patients enrolled in the clinical studies, which are necessary to secure product registrations worldwide.  Only with this focus can treatment ultimately be made available to all other  patients who need it.

Genzyme has received requests for rhGAA for patients who do not qualify for studies d1602 or 1702.  It is our hope that, at some point in the future, we may have enough of the enzyme to make it available to some patients on an expanded access basis.  At the moment, however, we must focus on using all available enzyme to conduct the clinical studies that we hope will demonstrate that rhGAA is efficacious and safe, so that we can apply for approval for medical use as soon as possible. 

Product Registration
Genzyme intends to seek product registrations globally and is continuing its discussions with regulatory authorities in Europe regarding the content and timing of a marketing authorization application.  We are pleased that these authorities recognize the urgent medical needs of Pompe patients and are working constructively with us to enable us to file for approval as quickly as is possible.  We hope to have these same discussions with regulatory authorities in the United States and other countries in the near future.

This document contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements including, among others, actual enrollment rates for clinical trials, the ability to produce sufficient product for development and commercialization activities, the timing and content of decisions by regulatory authorities, and risks, and uncertainties described in reports filed by Genzyme Corporation with the Securities and Exchange Commission under the The Securities Exchange Act of 1934, as amended, including without limitation Exhibit 99.2 to Genzyme's 2001 Annual Report on Form 10-K, as amended. Genzyme® is a registered trademark of Genzyme Corporation.

Genzyme’s Pompe Program Update
December 2002

Q:  What is the status of the Pompe program?

Genzyme has made strong progress within its Pompe disease program since its decision earlier this year to move forward with an internally developed product candidate.  In November, we filed an IND with the FDA for the first of several planned clinical studies, marking a significant milestone in our Pompe program.  We share with patients and their families a tremendous sense of urgency to begin clinical studies of  Genzyme’s recombinant human acid alpha-Glucosidase (rhGAA), so that we can move toward the goal of making a treatment broadly available.  Our discussions with regulatory authorities to date have been positive, and we are optimistic that they will support us in moving this process forward expeditiously.  The Pompe program is currently Genzyme’s largest research and development initiative.

Q:  When will new clinical trials begin?

Enrollment is expected to begin by the end of this year in the first of several planned clinical trials evaluating the use of rhGAA to treat
infantile-onset Pompe disease.  Patients up to three years old with the infantile-onset form of the disease will be included in this study.  A
second trial is expected to begin in the second quarter of 2003 and will focus on patients less than six months old with the most severe infantile-onset form of Pompe disease, in which infants generally die before the age of one year.  The studies—to be conducted at medical centers in the United States, Europe, and Asia once we receive the necessary regulatory and IRB approvals—will focus on the effect of treatment on patient survival, as well as other factors such as respiratory function, cardiac status, motor development, and safety.   Clinical studies for patients with late-onset Pompe disease are expected to begin once a sufficient supply of clinical trial material is available.

Q:  Are you able to make product available for compassionate use?

Sufficient quantities of Genzyme rhGAA are currently available to conduct the two planned infantile studies.  In addition, patients now receiving
either transgenic rhGAA or rhGAA licensed from Synpac (North Carolina) Inc. are scheduled to transition to Genzyme rhGAA next year.  Genzyme has held discussions with regulatory authorities regarding the current limitations on product supply and the urgent needs of Pompe patients.  Until adequate product inventory exists, priority must be given to maintaining patients who are currently on therapy and to conducting the clinical studies necessary to secure product registrations worldwide.  Only with this focus can treatment be made available as quickly as possible to patients who need it.

Q:  How is product manufacturing going?

Genzyme has successfully initiated production of rhGAA in its development-and pilot-scale manufacturing facilities in Framingham, Massachusetts.  In addition, Genzyme is now working to complete the installation of commercial-scale bioreactors at its Allston Landing manufacturing facility in Boston to provide capacity for rhGAA production in the longer term.

Q:  When do you expect to seek product registration?

Genzyme is continuing its discussions with regulatory authorities in Europe regarding the content and timing of a marketing authorization application. These discussions have not yet been held with regulatory authorities in the United States or other countries.

Q:  Have there been program management changes?

A:  Yes.  John Crowley, senior vice president, Genzyme Therapeutics, and general manager of the Pompe program, is leaving the company to spend more time with his family, particularly his children, both of whom suffer from Pompe disease.  Mr. Crowley came to Genzyme in 2001 following Genzyme’s acquisition of Novazyme Pharmaceuticals Inc., where he was president and chief executive officer.  He will continue to work with Genzyme as a consultant. Frank Ollington, Ph.D., senior vice president, Genzyme Therapeutics, has assumed management responsibility for the Pompe program. Frank has held a number of important leadership positions in his 14 years with Genzyme.  He directed the start-up of the Allston Landing manufacturing plant, served as president of the Genzyme Pharmaceuticals business unit and senior vice president of corporate operations, and chaired the steering committee overseeing the development of Aldurazyme® (laronidase), a product under development for the treatment of the genetic disorder MPS 1.

This document contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements including, among others, the risks and uncertainties described in reports filed by Genzyme Corporation with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation Exhibit 99.2 to Genzyme's 2001 Annual Report on Form 10-K, as amended.  These statements speak only as of the date of this document.  Genzyme® is a registered trademark of Genzyme Corporation.  Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC.  All rights reserved.

October 2nd 2002

Dear IPA members,

Herewith I would like to inform you about the IPA/Genzyme telephone conference of 
September 24 2002.

We discussed issues concerning the production, the transition, new trials and the meeting with the Erasmus University, VSN, Parents, patients and Genzyme. These issues will also be addressed in the presentation Genzyme will give on October the 12th at the AGSD meeting in Nottingham. Genzyme will give an update of the Pompe program and conduct a patient question and answer session. On October the 13th Genzyme representatives will attend the afternoon workshops of the IPA General Member meeting and discuss with the IPA representatives the Pompe program, and future collaboration between IPA and Genzyme.

The CHO product

First I would like to mention that Genzyme decided to turn to an internally developed CHO cell rhGAA, and to manufacture the product themselves. Genzyme has considerable experience with CHO-based manufacturing (Cerezyme, Fabrazyme, Thyrogen). Based on current experience, the Genzyme developed CHO rhGAA process is expected to provide a reliable clinical and commercial supply. In addition Genzyme expects to be able to scale-up this process as necessary to accommodate capacity needs as they arise.

New studies

Genzyme has a meeting scheduled to discuss clinical protocols for two new studies with the FDA in mid-October. During this meeting Genzyme hopes to receive input from the FDA on their new protocols. Genzyme's proposed studies will focus on the most severe infantile forms of the disease and will utilize the Genzyme CHO cell-derived rhGAA. These studies are currently envisioned to begin sometime before the end of the year.

The start dates will depend primarily on the availability of material and whether Genzyme receives necessary regulatory and trial site clearance to begin the studies. Genzyme is continuing with their preparations to submit an IND (Investigational New Drug) application to the FDA for their internally manufactured CHO cell-derived rhGAA.

The exact number of participants and the final inclusion criteria will not be finalized until the regulatory authorities have reviewed the study design.

Clinical trial site selection has not been finalized. Site selection criteria include issues such as finding investigators who have experience in conducting complex clinical trials and have the necessary facilities and resources to conduct the studies. In addition, each individual site's IRB (Institutional Review Board) or EC (Ethics Committee) must approve the study before it can begin. Various sites in the US, Europe and Asia are currently under consideration.

Production

Genzyme informed us that over the summer they made significant progress in addressing the need to increase manufacturing capacity for CHO cell-derived rhGAA. Genzyme has made modifications to the production of CHO cell-derived rhGAA and added new bioreactors as part of its continuing effort to address issues surrounding increasing supply.

Meeting in Rotterdam

On September 18, 2002, the Dutch patient organization, VSN, held an in-depth meeting between Genzyme, the treating physicians at Erasmus MC the parents of the patients and patients receiving the transgenic enzyme derived from rabbits' milk. It was a very constructive meeting. The Erasmus MC expressed their confidence in the efforts of Genzyme based on the information that was given.

Transition

This past summer patients were transitioned from the transgenically derived enzyme to the CHO cell-derived enzyme. Thus far, they had a smooth transition, with similar tolerance as with transgenic infusions. Patients will be followed closely by a group of treating physicians and Genzyme for safety and efficacy.

However, Genzyme guaranteed on July 26th that the three infantile patients in the Netherlands would continue to be treated with the transgenic enzyme until the spring of 2003 when the supply of transgenic enzyme is depleted.

In conclusion

At this moment enzyme-replacement therapy is a new experimental therapy. This will bring us uncertainties now and in the future. The therapy is not available for all the Pompe patients worldwide. First the therapy has to be approved and the CHO cell-derived enzyme has to be registered as a medicine and there has to be enough supply. Both processes take time. Valuable time. However we hope that the information above gives you an idea about the ongoing process of development of enzyme replacement therapy for people with Pompe´s disease.

With warmest regards,

Ria Broekgaarden
Secretary-IPA board

April 2002

IPA/Genzyme Meeting
April 16-17, 2002

Board members of the IPA, the International Pompe Association, met with key representatives of Genzyme in Cambridge, Massachusetts on April 16-17, 2002.  The IPA members in attendance were: Randall House, AMDA-US; Marylyn House, AMDA-US, Ria Broekgaarden, VSN-The Netherlands; Maryze Schoneveld van der Linde, VSN-The Netherlands; Bob Morrison, AMDA-Australia. 

Genzyme representatives included Jan van Heek, Executive Vice President; John Crowley, Senior Vice President of Therapeutics and General Manager of the Pompe Program; and numerous senior executives involved in pre-clinical, clinical, manufacturing, science, operations, product development, and patient advocacy.

We were extremely pleased with the extent of the information shared and with Genzyme’s candor in the dialogue that transpired.  Although the bulk of the information shared was highly confidential, we think it is important to provide you with a summary of what we have learned.

The following information was presented at the meeting:
Over the last 6 months, Genzyme has conducted comprehensive, blinded studies both in-house and in collaboration with independent investigators.  All four of the existing Pompe enzymes were placed into a comparative study.  The study included: the transgenic enzyme developed in joint venture with the Pharming Group N.V., which began in 1998; the CHO enzyme licensed from Synpac in 2000; the enzyme obtained in the Novazyme acquisition in 2001; and the internally produced CHO enzyme, that Genzyme began developing last year. 

Each enzyme was analyzed and compared. Data derived from these studies showed that the highest degree of glycogen clearance in the muscle cells was achieved with the CHO enzyme. This was substantiated at various dosages. Results were extremely comparable between the original CHO enzyme, licensed from Synpac, and the new CHO enzyme, produced in-house by Genzyme. Results showed that in glycogen clearance, there was a very similar, robust response between the two products. 

In addition, the data suggests that there is a high correlation between reduction in glycogen content and response to the introduction of ERT. The data derived from these studies will further support the filings with the regulatory authorities and continue to build upon what is already understood about Pompe and the potential benefits of ERT.

The results in the comparative studies have also supported Genzyme’s decision to shift further development from the Synpac CHO product to its own internally produced CHO derived enzyme. This step will allow Genzyme not only to gain better control of production but is also expected to yield more mature enzyme in a shorter period of time.  Shifting to the Genzyme produced CHO should ultimately lead to an increased supply of the drug, thus pursing best path forward for clinical and commercial use.

Genzyme’s development of the Novazyme NZ-1001 product, as a potential next-generation therapy for Pompe’s disease, is proceeding and continues to be in pre-clinical development.  It is intended that Novazyme's science, which focuses on targeting and uptake of enzyme, will continue to serve as a central component in the efforts to develop improved second-generation versions of the Pompe ERT, improve upon some of their current marketed products, as well as help to develop new therapies for the treatment of additional lysosomal storage disorders.

To date Genzyme has been able to produce only enough enzyme for those patients participating in the current clinical studies.  Genzyme’s Vice President of Manufacturing presented the plan for up-scaling the production of enzyme to provide enough product to support additional clinical studies and to work toward the goal of an expanded access program for patients severely affected and who do not meet future trial criteria.

To date enzyme has been produced in several 90-liter bioreactors and is currently being up-scaled into 160 liter bioreactors.  Genzyme has purchased a 2000-liter bioreactor (in excess of $5 million-US) which should be online by the end of the year.  In 2003 they will have a second 2000-liter bioreactor producing enzyme.  It is important to point out that each time production is up-scaled into a larger bioreactor, Genzyme must demonstrate to the regulating authorities that the new process does not change the make-up of the enzyme; thus, increasing supply is a timely process.

Genzyme will continue to supply the Synpac CHO product to patients participating in the extension of clinical trials of this product as it has done with patients receiving the transgenic enzyme. Eventually, all study participants will be transitioned to the Genzyme produced CHO enzyme.  This will occur only after additional laboratory testing is done to determine safety and equivalency of dosage, and after in-depth discussions with each patient’s physicians has been completed.

Genzyme also presented their clinical trial plan, designed to be the swiftest path forward to obtaining approval and bringing treatment to patients worldwide. The initiation of clinical trials will depend on the success of their production efforts and on the approval by the regulating authorities. They are anticipating the launch of several overlapping trials in the second half of 2002. 

They are planning on conducting extended and pivotal infantile trials, as well as trials including delayed onset patients (patients not diagnosed with the classical infantile form of Pompe). If approved, the future trials will be utilizing the Genzyme internal CHO enzyme. They are planning for the studies to be conducted in several centers between the US and Europe.  The inclusion criteria has not yet been finalized, and will not be considered finalized – and therefore made public - until regulatory approval to begin enrollment has been granted.  This is because, that until approval is granted to begin enrollment, every detail regarding their plan is up for discussion and could possibly need to be altered to comply with regulatory concern.

At the conclusion of these meetings, all of us in attendance felt that there had been much accomplished in the last several months.  We also believe that Genzyme is doing everything in their power to develop ERT as quickly as possible.  What we have learned is that there are so many more factors in developing an ERT than we previously recognized.  Although it seems like a long waiting period, right now, for the next set of studies, it should bring an approved treatment to all patients in an overall shorter amount of time. 

We recognize the importance of the comprehensive studies conducted by Genzyme in order to compare all forms of Pompe enzymes.  Data shared with us, that was derived from this study, substantiates Genzyme’s claim that they are pursuing the most efficient pathway to commercialization. This is based not only on manufacturing considerations, but on clinical analysis as well. This most important data will hopefully expedite both ERT and reimbursement approval.

In moving forward, we will continue to develop the Pompe public awareness program that is so important and about which many of you have voiced concerns. We are working to develop a plan of action for the IPA and our member organizations. We will share more detailed information on this front when the plan is more refined (in the next several weeks).  In addition, we will continue to keep the dialogue open with Genzyme through the bi-monthly teleconferences and will provide you with updates of those conversations.

We all agree that this meeting was a step forward in working together for what we all desire most….a safe, effective, and rapid treatment for all Pompe patients.

March 2002

Following is a letter sent to the IPA by Jan van Heek, Executive Vice President of Genzyme, for release prior to the VSN Pompe Patient Conference which took place on March 9, 2002. in the Netherlands.

Dear Friends,

On Saturday, March 9^th, 2002, I will be speaking at the VSN (The Dutch Muscular Dystrophy Association, Vereniging Spierziekten Nederland) Annual Patient Conference in The Netherlands. At the conference I will provide a general overview of Genzyme, focusing on our plans to move forward with the development of ERT (Enzyme Replacement Therapy) for Pompe disease. In an effort to keep you informed I would like to share with you some of the highlights of my presentation.

First, thank you for your patience over the last six months as we have made dramatic and significant advancements in the Pompe development program. Genzyme has fundamentally reorganized the structure, organization and leadership of Genzyme’s global Pompe efforts. Twelve key members from the executive teams of Genzyme and Novazyme (a fully owned subsidiary of Genzyme as of 11/15/01) have formed the PLT (Pompe Leadership Team), chaired by John Crowley. We have engaged the best and the brightest individuals in the PLT to move this program forward as quickly as possible. The PLT sets the strategic direction and is responsible for making operational decisions with respect to all aspects of the Pompe program, including: pre-clinical, manufacturing, clinical, regulatory, and business, along with input from Genzyme’s senior executives.

We truly believe that 2002 will finally mark the year of change for the future of Pompe patients worldwide.

In the past, one of the vexing problems has been limited supply of the protein for ERT. We have made significant improvements in both the quantity and quality of enzyme production over the past months. We have transitioned all enzyme production into Genzyme’s own manufacturing facilities and have much more control over enzyme quality, consistency and quantity. We are confident that our manufacturing process changes will ensure adequate product supply in the future.

We will soon be meeting with the regulatory authorities to discuss specific details of the next clinical studies of our CHO cell line product in different patient groups. The specific numbers of patients and inclusion criteria have not yet been presented to the regulatory authorities and therefore, are not yet finalized. Presently, we plan that this will be a multi-center, international trial, with sites in both Europe and the United States.

We will disclose more details about the inclusion criteria, specific timeline and overall design of the trial when we receive approval from the regulatory authorities. We anticipate enrolling patients into the new trials as soon as we conclude our discussions with the regulatory authorities.

Please note that the safety and efficacy of our CHO cell line ERT for Pompe disease has not yet been established in large clinical studies. As part of this aggressive development plan we plan to accumulate a strong package of pre-clinical and clinical evidence to present to the regulatory authorities in the future.

In closing, I would like to emphasize that our goal is to have both an approved and reimbursed product available to all patients around the world. To achieve this task we need to work together to generate a greater awareness about the life-threatening affects of Pompe disease.

Many patients ask what they can do to help. My response is to ask you to work within your local areas to generate public interest stories focused on Pompe. The more we can raise awareness and recognition of Pompe disease. There is still much work to be done, but by working together we can ensure that the future for individuals and families affected by Pompe will be bright.

At this time I respectfully ask for your continued patience for several more weeks until our discussions with the regulatory authorities are concluded. At that time we will share with you the approved clinical path forward for 2002. In the meantime please direct any questions you may have to Sara Den Besten, Senior Manager of Patient Advocacy (email: sdenbesten@novazyme.com - phone: (609) 683 – 4400 x119).

Sincerely,

Jan van Heek
Executive Vice President, Therapeutics and Genetics
Genzyme Corporation

(Released March 5, 2002)

Mr. van Heek was unable to attend the VSN Conference on March 9, 2002, as initially planned. Philippe van Holle and Dr. Cabri addressed the group in his absence.

Letter from Randall House, IPA Chairman to Pompe Patients

The International Pompe Association (IPA) board will meet on February 18-19th, 2002. Representatives of scientific/medical teams and Genzyme will attend. The following issues will be discussed:

1. Finalize the universal patient questionnaire to be distributed in the near future by the IPA to all member organizations throughout the world.

This questionnaire is a long-time endeavor by leading researchers in the Pompe field. It will serve a two-fold purpose:

A. To identify and classify Pompe patients worldwide
B. To serve as an independent patient database

This database will safeguard patient confidentiality, but will also allow accessibility to data by corporations, physicians, and medical facilities working towards treatments for Pompe's disease.

2. Compassionate (or humanitarian) use will be discussed. The objective is to set up criteria for making enzyme replacement therapy available to patients before market approval is obtained.

Availability of enzyme is the critical issue in this agenda--how to make the currently produced enzymes available to more patients in the shortest possible time. This matter (expanded production) will be a major point of discussion with Genzyme representatives at this meeting.

3. Current results from the ongoing clinical trials (CHO and transgenic) and the current timetable for initiation of new CHO trials will be discussed.

4. Collaboration between IPA and Genzyme to release research and development information on a quarterly basis to patient organizations.

5. Expense of enzyme replacement therapy (when marketed) will be discussed--how to insure that the cost will not prohibit any patient from receiving treatment.

Be assured that patient organizations through the IPA are working with Genzyme as well as with Pompe researchers to continue to push for safe, effective, and timely treatment for all patients with Pompe's disease.

Best Regards,
Randall House
President, IPA

February 2002

IPA Board Meeting-----February 18-19, 2002

The first official IPA Board Meeting occurred in Rotterdam, The Netherlands on Feb. 18-19, 2002. Future agendas were planned and the following committees were formed:

1. Communications—Kevin O’Donnell, Alan Muir, Marylyn House

2. Patient Organizations—Maryze Schoneveld, Marylyn House

3. Legal Issues—Helmut Erny, Ria Broekgaarden

4. Financial Budget and Sponsoring—Randall House, Helmut Erny

5. Scientific/Industrial Contacts—Randall House, Bob Morrison, Ria Broekgaarden

Issues discussed were:

1. Expansion of the existing trials

2. New trials

3. Product supply

4. Compassionate/humanitarian use

5. Product registration

6. Reimbursement

7. Timetable of future events. Genzyme has agreed to supply IPA with a detailed progress report on a quarterly basis.

IPA Patient Questionnaire*:
The IPA patient questionnaire will be ready for distribution to the member organizations by the end of the month. Accurate translation of the questionnaire and how to safeguard patient confidentiality was discussed. The first versions for distribution to patients will be available in English and Dutch.

--------------------------------------------

*The purpose of the questionnaire is to gather data in order to classify patients by onset, symptoms, muscle strength, respiratory functions, family history, progression of the disease, mutation, etc. Patient confidentiality will be maintained by a coding system which will allow the IPA to provide equal access of statistical data to researchers, medical institutions, and corporations involved in Pompe research and treatment.

The information on the questionnaire will help researchers learn more about the progression of the disease in order to "fit" patients into categories based on similarities. This will help researchers determine the "path" of illness and the progression of the disease and thereby maximize the efficiency of ERT and future treatments. Participation or non-participation in the questionnaire study will in no way influence a patients participation in clinical trials for Pompe's disease.

The questionnaire was developed mainly through the endeavors of Dr. C. Loosen, M.D., Ph.D., Rotterdam, The Netherlands. Dr. Loonen, a pediatric neurologist, is an expert in the field. She has been involved in Pompe research for over 30 years and has published numerous articles on the disease.

--------------------------------------------

Following is a summary of the meeting--February 18-19, 2002 

by Alan Muir (ASGD-UK):

The IPA (International Pompe Association) meeting of February 18-19, 2002, was chaired by Randall House (AMDA-US). Those present were: Allan Muir (AGSD-UK), Ria Broekgaarden (VSN), Maryze Schoneveld (VSN), Anton Hammink (VSN), Helmut Erny (SHG Glydogenose Deutschland e.V.). The secretary was Paula Waddell, (VSN). Bob Morrison (AMDA-Australia) joined the meeting via telephone hook-up.

The main points of the two days were as follows:

1) The IPA (International Pompe Association) constitution was agreed to by those present. Board members were nominated and executive positions filled. Ria Broekgaarden will organize the signing of the constitution and other managerial matters.

2) The IPA (International Pompe Association) membership now extends to 27 countries headed by interested groups/persons who represent some 680 Pompe's patients worldwide.

3) The questionnaire, to be used for compiling the Pompe's Registry, has been completed and agreed to by professionals, expert in the Pompe field. It now needs to be translated into the appropriate languages before being issued to the support groups for distribution to patients.

During the evening of the 18^th, Dr. Ans van der Ploeg and Dr. Arnold Reuser were invited to talk about the on-going clinical trials, and Dr. Patrick Cabri, Genzyme Europe, gave a presentation on the ERT registration process in Europe.

Dr. van der Ploeg had little additional news from the current trials in Rotterdam. She did, however, say that ERT should not be considered alone in the treatment of Pompe's. For good recovery, it must be part of a good rehabilitation program including physiotherapy and other practical training. She added that keeping as healthy as possible prior to ERT is also important; the therapy is most effective with those patients least affected.

Dr. Cabri, Genzyme-Europe, provided the following information:

1. Dr. Cabri described the procedure for achieving drug approval in Europe by the EMEA, the European Agency for the Approval of Medicinal Products. A dossier is currently being compiled from all the research and trials and will (soon?) be submitted. Approval will take at least 12 months. The dossier will be presented for scientific scrutiny to 15 countries. After approval through EMEA, Genzyme must seek national approval (in Europe). This can take 1 to 24 months. It is important that the national government offices be aware of the drug before its submission to save valuable time.

2. Compassionate use was discussed, and Dr. Cabri stated that once ERT is licensed (this is prior to universal marketing of the drug) for use in a country, it will be up to a patient's physician to apply for the drug on compassionate grounds. However the acceptance criteria is likely to be quite harsh (e.g. must be life-threatening situation). Genzyme is currently working on a development plan - which includes proposals for compassionate use. An announcement on this is expected 'soon'.

3. Approval by the US-FDA was also brought up. Basically the same timetable should apply for the approval process in the US. Genzyme is working towards approval in the US and Europe simultaneously.

4. Availability of the ERT is likely to be another issue as there is currently a worldwide shortage of fermenters. Production facilities in the US have room for expansion, but many other orphan drugs in development
   will be competing for their use --short term (next 5 years). This is a real problem, but it is being aggressively addressed by Genzyme.

July 1999

IPA--International Pompe Association
First IPA Conference Held July 2-4, 1999

The first IPA Conference was held on July 2-4, 1999, in Naarden, the Netherlands. The meeting was attended by over 60 participants from 11 countries which included members of the medical and scientific community, patient organizations and industry. Presentations included a historical overview of Pompe’s disease, ongoing research in enzyme replacement and gene therapy, and presentations from patient organizations. Randall H. House, president of AMDA (USA), chaired the first day’s proceedings. Y.S. Poortman, president of VSN (the Netherlands) opened the conference and welcomed the guests.

The opening presentation was given by Dr. M.C.B. Loonen. Dr. Loonen served as Head of the Child Neurology Department of the Academic Hospital Rotterdam, the Netherlands, from 1971 until retirement in 1995. Her thesis entitled, "The variability of Pompe’s Disease. A clinical, biochemical and genetic study of glycogen storage disease type 2, or acid maltase deficiency", appeared in 1979.

Dr. Loonen’s presentation gave a historical overview of Pompe’s disease from it’s initial description by J.C. Pompe, a Dutch pathologist in 1932; the discovery of lysosomes in 1955 by Christian de Duve (et al); the discovery by H. G. Hers (et al) that glycogen storage was caused by the deficiency of the lysosomal enzyme, acid alpha-glucosidase and his unsuccessful attempt at enzyme replacement therapy in 1963; the 1964 demonstration by Baudhuin (et al) which showed that glycogen stored in the liver of Pompe patients was present mainly within the lysosomes. In 1965 it was recognized that there are also "late-onset" forms of Pompe’s disease.

Although presently retired, Dr. Loonen is still involved in the clinical trials for enzyme replacement therapy currently underway at Sophia Children’s Hospital in Rotterdam.

Dr. M.G.E.M. Ausems, Clinical Geneticist and Head of Genetic Counseling in the Department of Medical Genetics, University Medical Center Utrecht, the Netherlands, based her presentation on her publication "The frequency of Glycogen Storage Disease type II in the Netherlands; implications for diagnosis and genetic counseling." (Ausems MEM, Verbiest J. Herman MMP, it al; Eur J Hum Genet in press).

Since 1995 she has been involved in studies on the frequency of Pompe’s disease and genotype-phenotype correlations of the disease in close collaboration with Dr. Reuser, Dr. van der Ploeg and Prof. Dr. J.H.H. Wokkel, Department of Neurology, University Medical Center Utrecht, the Netherlands.

Dr. Ausems’s data predicts that frequency of GSD II is 1 in 40,000 in the Dutch population as opposed to the frequently quoted figure of 1 in 100,000. A recent study on the carrier frequency by Frank Martiniuk, Ph.D., New York University Medical Center (USA), also indicated a disease frequency of 1 in 40,000, based on his study of the general population in New York (Martiniuk F, Chen A, Mack A et al. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. AM J Med Genet 1998; 79:69-72.)

Dr. Ausems concluded, "Our results suggest that the world wide frequency of GSD II must be higher than 1 in 100,000 and that the birth prevalence of adult GSD II is two times higher than that of infantile GSD II.

Prof. Dr. John J. Hopwood, Deputy Head of the Chemical Pathology Services and Head of the Lysosomal Disease Research Unit, Women’s and Children’s Hospital, North Adelaide, South Australia, stressed the importance of joining together all LSD, lysosomal storage disorders (of which there are 40), to broaden the patient base and thereby, bring this category of disorders to the foreground. Based on his research he has found that LSD affects approximately 1 in 5,000.

For over 20 years Dr. Hopwood’s research has been linked to the provision of a diagnostic service and the development of therapy for patients with LSD. Specifically toward GSD II he stated, "We have been developing new methodology to achieve fast, inexpensive and non-invasive procedures for the early detection and diagnosis of GSD II in individuals from newborns to adult populations," but he went on to say that diagnosis of GSD II using blood samples is complicated by the presence of other alpha-glucosidase activities.

Arnold J.J. Reuser, Ph.D., Associate Professor of Cell Biology, Department of Clinical Genetics, Erasmus University Rotterdam, the Netherlands, also made a historical presentation on Pompe’s disease.

Dr. Reuser has been involved in Pompe research since 1973. Throughout the 80s and 90s, he was involved in the biosynthesis and structure of acid alpha-glucosidase, the cloning of the acid alpha-glucosidase gene, mutation analysis, and the development of a mouse model for Pompe’s disease. All of these endeavors have lead to the commencement of clinical trials in enzyme replacement therapy for Pompe’s disease currently in progress at Sophia Children’s Hospital in Rotterdam.

Dr. Reuser joined Professor Hans Buller, director of Sophia Children’s Hospital Rotterdam, and Dr. Ans van der Ploeg, principal investigator, who recently expressed their optimism about the progress of the trial.

Dr. Reuser concluded by ".......highlighting the role of the patients, patient organizations and charities that have kept the ‘process’ alive. Our research team.......has experienced tremendous support.......from patients.......(and) patient organizations and charities (such as), the AGSD (UK), the AMDA (USA), the Prinses Beatrix Fonds and the Sophia Foundation, in particular, .......(who) have made financial contributions to keep us going." He closed his speech by commending the formation of the IPA.

Dr. Andrea Amalfitano, Duke University Medical Center (USA) made a presentation entitled "Therapy for GSD-II; Enzyme based therapeutics and novel gene therapy approaches."
(see research from Duke June 25, 1999 & Aug. 3, 1999)

Dr. A.T. van der Ploeg, Sophia Children’s Hospital Rotterdam, The Netherlands, gave her presentation entitled "Enzyme therapy for Pompe’s disease" on the last day of the conference.
see Phase II Juvenile Trials Underway in Netherlands, July 4, 1999

Presentations were also made by industry representatives:

"A Transgenic Approach to Enzyme Replacement Therapy in Pompe Patients" was jointly made by A. Vos, Ph.D., Pharming/Genzyme LLC (Netherlands); J. Dalle, MSc, Pharming NV (Belgium); A. Curtis, MBA, Genzyme Corp (USA).

"The Challenges of rhGAA Manufacture " was the title of the presentation made by Blythe Devlin,Ph.D., Synpac (N.C.) Inc.

Patient organization presentations included the following:

"Knowledge is power" and "The importance of good information," Kevin O’Donnell, Ph.D., AGSD (UK);

"Forming a national Pompe group, our experience," Marylyn House, AMDA (USA);

"The International Pompe Association, position, objectives, policy and activities," Ysbrand Poortman, VSN (Netherlands); "Developments in the area of Pompe’s disease," Haske van Veenendal, VSN (Netherlands);

"Funding treatment before the government subsidy approvals," Robert Morrison, MDA (Australia);

"Legal procedures regarding the International Pompe Association," Helmut Erny, SHG Glycogenose Deutschland eV(Germany)

Maryze Schoneveld van der Linde, representative of VSN, presented a moving autobiographical portrait of a Pompe patient’s endurance of this progressive debilitating disease. Maryze has struggled with the juvenile form of the disease for over 20 years. She was diagnosed with the disease at the age of 8. Her speech was entitled "From patient initiative to treatment."

Ria Broekgaarden, VSN, and Randall House, AMDA, co-chaired the second day’s events. Thomas Schaller, SHG Glykogenose Deutschland (Germany) chaired the final day’s session.

A closed session to formulate and discuss IPA objectives was co-chaired by Randall House and Ysbrand Poortman and included only members of patient groups. Mr. House summarized the committee report at the general meeting on the final day.

The IPA homepage can be reached at:  http://www.worldpompe.org

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