Joint Statement following April 2002 Meeting

Category: Archive
April 16, 2002

On 16/17 April, 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.

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