Genzyme Pompe Program Update February 18, 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.
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) atfive research hospitals (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 H=F4pital 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 trial (study 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 rhGAA is available.
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 supportpatients 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 millionsof 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. 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 1602 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.
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 andare 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 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=AE is a registered trademark ofGenzyme Corporation.