FDA Approves Genzyme's Myozyme® for All Patients with Pompe Disease Genzyme Corp. (Nasdaq: GENZ) announced today that the Food and Drug Administration has granted marketing approval for Myozyme® (alglucosidase alfa) in the United States. Myozyme has been approved for the treatment of patients with Pompe disease, a debilitating, progressive and often fatal disorder affecting fewer than 10,000 people worldwide. The product is the first treatment ever approved for Pompe disease and the first for an inherited muscle disorder. "This is a special day for people across the Pompe community and at Genzyme, who have worked together for many years and overcome enormous challenges so that patients with this devastating disease now have a chance," said Henri A. Termeer, chairman and chief executive officer of Genzyme Corp. The Myozyme label includes the following indication: "Myozyme (alglucosidase alfa) is indicated for use in patients with Pompe disease (GAA deficiency). Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy." The product label also includes a boxed warning with information on the potential risk of hypersensitivity reactions associated with Myozyme. The boxed warning states that "Life-threatening anaphylactic reactions, including anaphylactic shock, have been observed in patients during Myozyme infusion. Because of the potential for severe infusion reactions, appropriate medical support measures should be available when Myozyme is administered." Of the 280 patients who received Myozyme in clinical studies or through expanded access, eight patients (3 percent) experienced severe or significant hypersensitivity reactions. Full prescribing information for the product is available on Genzyme's Web site. Pompe disease manifests as a broad spectrum of clinical symptoms. All patients typically experience progressive muscle weakness and breathing difficulty, but the rate of disease progression can vary widely depending on the age of onset and the extent of organ involvement. When symptoms appear within a few months of birth, babies frequently display a markedly enlarged heart and die within the first year of life. When symptoms appear during childhood, adolescence or adulthood, patients may experience steadily progressive debilitation and premature mortality due to respiratory failure. They often require mechanical ventilation to assist with breathing and wheelchairs to assist with mobility. Genzyme recently completed enrollment in its clinical trial involving patients with late-onset Pompe disease. Ninety patients have been enrolled in this international, placebo-controlled study. Currently, more than 280 patients in 30 countries are receiving Myozyme through clinical trials, expanded access programs, or pre-approval regulatory mechanisms. Myozyme has received orphan drug designation in the United States, which provides seven years of market exclusivity. The orphan drug law is designed to encourage the development of treatments for rare disorders such as Pompe disease, for which no therapies have existed previously. Genzyme expects to launch Myozyme in the United States within two weeks. Late last month, Myozyme was approved in the European Union. Because early diagnosis, intervention and treatment are critical in Pompe disease and other lysosomal storage disorders, Genzyme has for the past seven years supported several outside research collaborations to develop new diagnostic technology. This research has led to the recent introduction of an enzyme assay utilizing blood samples that makes it possible to diagnose Pompe patients more rapidly and with a less-invasive procedure. Genzyme will offer this test now through its Genzyme Genetics unit, and the test will also be available through several other clinical laboratories in the United States and elsewhere in the world. "The journey from development to approval of a therapy for Pompe disease has been a long and winding road, but we are now at a milestone and are thrilled with the outcome," said Randall H. House, chairman of the International Pompe Association and president of the Acid Maltase Deficiency Association (AMDA), a Pompe patient association in the United States. "Enzyme replacement therapy with Myozyme gives Pompe patients hope." The AMDA, formed in 1995, has assisted in funding Pompe disease research and promotes public awareness of Pompe disease. Valerie Cwik, medical director for the Muscular Dystrophy Association, said: "Myozyme is the first treatment for any of the muscle diseases included among the 40 neuromuscular disorders covered by the Muscular Dystrophy Association. This is a great day for people with Pompe disease, and a hopeful moment for the thousands of other people who are affected by the diseases in the MDA program, because it shows that support and research can lead to treatments." The MDA helped support patients who took part in clinical trials of Myozyme and also sponsored early research in Pompe disease. Genzyme began working to develop a treatment for Pompe disease in 1998. In 2003, the company initiated a pivotal clinical study of Myozyme that demonstrated the product's safety and efficacy. In the study, 83 percent of patients treated with Myozyme were both alive and free of invasive ventilator support at 18 months of age. In a natural history study, 2 percent of similar infantile-onset patients were alive at 18 months of age. The pivotal trial enrolled 18 patients with infantile-onset Pompe disease, who began receiving therapy at approximately six months of age. The most common serious adverse events observed in clinical studies of Myozyme, whether or not they were related to the drug, were pneumonia, respiratory failure, respiratory distress, catheter-related infection, respiratory syncytial virus infection, gastroenteritis and fever. Many of these can be complications of Pompe disease. "We are very proud that we have been able to bring to market four therapies for ultra-orphan diseases where no treatments existed previously," said Mr. Termeer. "This underscores our fundamental commitment to patients and confirms the productivity of our research efforts. We continue to invest in potential new approaches to treating these diseases." Myozyme is the fourth enzyme replacement therapy developed by Genzyme for a rare genetic disease. Genzyme has developed Cerezyme® (imiglucerase for injection) for Type 1 Gaucher disease; Fabrazyme® (agalsidase beta) for Fabry disease; and, in collaboration with BioMarin Pharmaceutical Inc., Aldurazyme® (laronidase) for MPS I. These treatments are currently available to patients throughout the world. Genzyme currently manufactures Myozyme in the United States. In the future, the company expects to also produce Myozyme at its new protein manufacturing facility in Geel, Belgium, and its new fill/finish facility in Waterford, Ireland, to ensure that it is able to meet the anticipated demand for the product throughout the world. About Pompe Disease Pompe disease, also known as Acid Maltase Deficiency or Glycogen Storage Disease Type II, is one of more than 40 genetic diseases called lysosomal storage disorders, which are caused by a deficiency or malfunction of specific enzymes found in cell lysosomes. People born with Pompe disease have an inherited deficiency of an enzyme known as acid alpha-glucosidase (GAA). Enzymes, which are protein molecules within cells, trigger biochemical reactions in the body. In a healthy person with normal GAA activity, this particular enzyme would assist in the breakdown of glycogen, a complex sugar molecule stored within a compartment of the cell known as the lysosome. But in Pompe disease, the GAA activity may be dramatically reduced, dysfunctional, or non-existent, resulting in an excessive accumulation of glycogen in the lysosome. Eventually, the lysosome may become so clogged with glycogen that normal cellular function is disrupted and muscle function is impaired. Although there is glycogen storage in the cells of multiple tissues, heart and skeletal muscles are usually the most seriously affected. For more information on Pompe disease, please visit www.pompe.com For information on Myozyme ordering and support services please call (800) 745-4447 or (617) 768-9000. About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. This year marks the 25th anniversary of Genzyme's founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,000 employees in locations spanning the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by FORTUNE as one of the "100 Best Companies to Work for" in the United States. With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as heart disease and other areas of unmet medical need. This press release contains forward-looking statements regarding the anticipated timing of a Myozyme launch, plans to launch a diagnostic test for Pompe disease, and the expected addition of Myozyme manufacturing sites. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected, including our ability to successfully identify and market to new patients; the timely receipt of pricing and reimbursement approvals in approved countries; our ability to enter into agreements with our distributors; scientific, technical and manufacturing issues that could prevent the successful launch of the Pompe diagnostic test, the failure of the test to produce diagnostic results as anticipated; the commercial acceptance of the diagnostic test, including the acceptance of the diagnostic test at price levels that are economically viable for Genzyme Genetics; and our ability to produce Myozyme at our Geel, Belgium facility or produce it in sufficient quantities to meet demand. Please refer to the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Annual Report on Form 10-K for the year ended December 31, 2005 for a more complete discussion of the risks associated with Genzyme's business. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements. Genzyme® and Myozyme® are registered trademarks of Genzyme Corporation. All rights reserved. European Commission Approves Genzyme's Myozyme® Product is First Treatment for Pompe Disease Genzyme Corp. (Nasdaq: GENZ) announced today that it has received marketing authorization for Myozyme® (alglucosidase alfa) in the European Union. Myozyme has been approved for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Pompe disease, a debilitating, progressive and often fatal disorder affecting fewer than 10,000 people worldwide. The product is the first treatment ever approved for Pompe disease and one of the first for an inherited muscle disorder. "This is an extraordinary moment for Pompe patients and their families," said Henri A. Termeer, chairman and chief executive officer of Genzyme Corp. "The effort to develop Myozyme has required the enormous commitment of many people throughout Genzyme and across the Pompe community, who have worked with a great sense of urgency and have overcome tremendous challenges. Our focus now is to ensure that Myozyme is available to all patients who need treatment." Myozyme has received orphan medicinal product designation in Europe. The orphan medicinal products regulation is designed to encourage the development of treatments for rare disorders such as Pompe disease, for which no therapies have existed previously. Genzyme will introduce Myozyme in Europe on a country-by-country basis, as pricing and reimbursement approvals are obtained. Ria Broekgaarden, of the Dutch Pompe patient organization VSN (Vereniging Spierziekten Nederland) and secretary of the International Pompe Association, said, "For people with Pompe disease, this is a very important moment in history. The approval of this treatment represents great hope and progress for all Pompe patients, which in turn will give them a new perspective on their future." Pompe disease manifests as a broad spectrum of clinical symptoms. All patients typically experience progressive muscle weakness and breathing difficulty, but the rate of disease progression can vary widely depending on the age of onset and the extent of organ involvement. When symptoms appear within a few months of birth, babies frequently display a markedly enlarged heart and die within the first year of life. When symptoms appear during childhood, adolescence or adulthood, patients may experience steadily progressive debilitation and premature mortality due to respiratory failure. They often require mechanical ventilation to assist with breathing and wheelchairs to assist with mobility. Genzyme began working to develop a treatment for Pompe disease in 1998. In 2003, the company initiated clinical studies of Myozyme, which produced highly encouraging results and formed the basis of the company's regulatory submissions. In the pivotal clinical study, 83 percent of patients treated with Myozyme were both alive and free of invasive ventilator support at 18 months of age, compared with two percent of patients in the historical cohort. The trial, which met its primary endpoint, enrolled 18 patients with infantile-onset Pompe disease, who began receiving therapy at approximately six months of age. Approximately 39 percent of patients treated with Myozyme developed infusion associated reactions, which were mostly mild to moderate in nature. Two patients experienced serious infusion reactions. One experienced urticaria, the other experienced urticaria, rales, tachycardia, decreased oxygen saturation, bronchospasm, tachypnea, periorbital edema and hypertension. Genzyme recently completed enrollment in its clinical trial involving patients with late-onset Pompe disease. Ninety patients are participating in this international, placebo-controlled study. Currently, more than 270 patients in 30 countries are receiving Myozyme through clinical trials, expanded access programs, or pre-approval regulatory mechanisms. Genzyme manufactures Myozyme at two facilities in the United States. To ensure that it is able to meet the anticipated demand for the product in Europe and throughout the world, the company expects to also produce Myozyme in the future at its new protein manufacturing facility in Geel, Belgium, and its new fill/finish facility in Waterford, Ireland. About Pompe Disease Pompe disease, also known as Acid Maltase Deficiency or Glycogen Storage Disease Type II, is one of more than 40 genetic diseases called lysosomal storage disorders, which are caused by a deficiency or malfunction of specific enzymes found in cell lysosomes. People born with Pompe disease have an inherited deficiency of an enzyme known as acid alpha-glucosidase (GAA). Enzymes, which are protein molecules within cells, trigger biochemical reactions in the body. In a healthy person with normal GAA activity, this particular enzyme would assist in the breakdown of glycogen, a complex sugar molecule stored within a compartment of the cell known as the lysosome. But in Pompe disease, the GAA activity may be dramatically reduced, dysfunctional, or non-existent, resulting in an excessive accumulation of glycogen in the lysosome. Eventually, the lysosome may become so clogged with glycogen that normal cellular function is disrupted and muscle function is impaired. Although there is glycogen storage in the cells of multiple tissues, heart and skeletal muscles are usually the most seriously affected. For more information on Pompe disease, please visit http://www.pompe.com/ About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. This year marks the 25th anniversary of Genzyme's founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,000 employees in locations spanning the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by FORTUNE as one of the "100 Best Companies to Work for" in the United States. With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as heart disease and other areas of unmet medical need. This press release contains a forward-looking statement regarding Myozyme manufacturing. This statement is subject to risks and uncertainties that could cause actual results to differ materially from those projected, including that Genzyme is unable to produce Myozyme at its Geel, Belgium facility or produce it in sufficient quantities to meet demand. Please refer to the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Annual Report on Form 10-K for the year ended December 31, 2005 for a more complete discussion of the risks associated with Genzyme's business. Genzyme cautions investors not to place substantial reliance on the forward-looking statement contained in this press release. This statement speaks only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statement. Genzyme® and Myozyme® are registered trademarks of Genzyme Corporation. All rights reserved. Genzyme Provides Update on U.S. Marketing Application for Myozyme® Genzyme Corp. (Nasdaq: GENZ) announced today that the Food and Drug Administration has extended by 90 days the review period for the biologics license application for Myozyme® (alglucosidase alfa). The new action date for the application is April 28, 2006. The purpose of the extension is to provide the FDA with sufficient time to review additional information submitted by Genzyme in late December at the agency's request. "This is a brief extension of the review period, and we continue to expect that Myozyme will be approved in the United States during the first half of this year," said Alison Lawton, Genzyme's senior vice president for regulatory affairs. "We have worked closely with the FDA throughout the review process and are confident the agency recognizes the urgency of making this treatment available to patients." Myozyme has been developed for the treatment of Pompe disease, a debilitating, progressive and often fatal muscular disorder. Genzyme submitted a biologics license application for Myozyme in late July. The application was given Priority Review status, which required the FDA to act within six months. Genzyme is currently engaged in a broad range of activities to prepare for Myozyme's introduction in the United States and in Europe, where the Committee for Human Medicinal Products is expected to issue an opinion later this month on the marketing authorization application for Myozyme. Approximately 200 patients in 14 countries are currently receiving Myozyme through clinical trials, expanded access programs, or pre-approval regulatory mechanisms. About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. This year marks the 25th anniversary of Genzyme's founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,000 employees in locations spanning the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by FORTUNE as one of the "100 Best Companies to Work for" in the United States. With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as heart disease and other areas of unmet medical need. This press release contains forward-looking statements regarding the expected timing of U.S. and European regulatory action on Myozyme. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. These risks and uncertainties include that the FDA may not approve Myozyme on the timeframe anticipated by Genzyme or at all. Please refer to the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Quarterly Report on Form 10-Q for the period ending September 30, 2005, for a more complete discussion of the risks associated with Genzyme's business. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements. Genzyme® and Myozyme® are registered trademarks of Genzyme Corporation. All rights reserved. Genzyme Submits BLA for Myozyme® for Treatment of Pompe Disease Genzyme Corp. (Nasdaq: GENZ) announced today that it has submitted a biologics license application (BLA) to the U.S. Food and Drug Administration for Myozyme® (alglucosidase alfa). If approved, Myozyme would be the first treatment developed for patients with Pompe disease, a debilitating and often fatal muscle disorder resulting from an inherited enzyme deficiency. The Myozyme BLA is expected to receive Priority Review by the FDA, which means the agency would be required to act on the application within six months. The BLA contains data from several clinical trials, including the pivotal study AGLU01602, which Genzyme reported today met its primary endpoint. This trial enrolled 18 patients with infantile-onset Pompe disease who began receiving Myozyme by six months of age. Outcomes for these patients were compared with a historical cohort, rather than a placebo cohort, because of the rapidly progressive and fatal nature of infantile-onset Pompe disease. All patients treated with Myozyme were alive at 18 months of age, compared with two percent of patients who were alive at this age in the historical cohort. The primary endpoint for the study was the proportion of patients treated with Myozyme who were both alive and free of invasive ventilator support at 18 months of age, compared with the proportion of patients in the historical cohort who were alive at 18 months of age. Eighty-three percent of patients treated with Myozyme (15 of 18) were both alive and free of invasive ventilator support at this age, compared with two percent of patients in the control group who were alive. "This is a very exciting and hopeful moment for Pompe patients and their families," said Henri A. Termeer, chairman and chief executive officer of Genzyme. "Myozyme could be available in the United States and Europe by the early part of next year and in other parts of the world relatively soon afterward." Genzyme will submit results from study AGLU01602 to the European Medicines Agency, which is reviewing a marketing authorization application for Myozyme filed in December 2004. The company anticipates submitting a marketing application for Myozyme in Japan later this year. Genzyme is seeking approval for Myozyme's use as a long-term enzyme replacement therapy for all patients with a confirmed diagnosis of Pompe disease, defined as a deficiency of the enzyme acid alpha-glucosidase. There is currently no approved treatment for the disease. Myozyme has received orphan drug designation in the United States, which would convey a seven-year period of market exclusivity if the product is approved. Orphan drug designations have also been granted in the European Union and Japan. More than 130 patients are now receiving Myozyme in clinical studies, through Genzyme's expanded access program, or through pre-approval mechanisms sponsored by governments in several European countries. Genzyme expects to initiate a clinical trial shortly for patients with late-onset Pompe disease. The company recently concluded an observational study involving late-onset patients, which was designed to evaluate appropriate endpoints for a treatment study. The Myozyme program is Genzyme's largest research and development initiative. About Pompe disease Pompe disease is an inherited, progressive muscle disease that affects fewer than 10,000 people worldwide. The disease is caused by a deficiency of an enzyme known as acid alpha-glucosidase. This deficiency leads to the excessive accumulation of glycogen in the body, particularly in the muscles. Pompe disease manifests as a broad spectrum of clinical symptoms with varying rates of disease progression. Infantile-onset patients present in the first months of life with an enlarged heart and skeletal and respiratory muscle weakness, and most die from cardiac or respiratory complications by one year of age. Late-onset patients may present with muscle or respiratory weakness anytime during childhood or adulthood, and disease progression is less rapid. Late-onset patients often require mechanical ventilation for breathing assistance and mobility aids such as canes, walkers or wheelchairs. Late-onset patients will experience a shortened lifespan due to progressive respiratory failure. Pompe disease belongs to a family of more than 40 rare inherited diseases known as lysosomal storage disorders. About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Founded in 1981, Genzyme has grown from a small start-up to a diversified enterprise with 2005 revenues expected to exceed $2.6 billion and more than 7,600 employees in locations spanning the globe. With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields as well as heart disease and other areas of unmet medical need. This press release contains forward-looking statements, including statements about clinical trial results, regulatory plans and expected timelines for Myozyme, including the submission of the AGLU-01602 trial study report to US and EU regulatory authorities, the submission of a marketing application in Japan and the timing thereof, the anticipated timing of commercial availability of Myozyme, and plans to initiate a clinical trial for late-onset Pompe patients and the timing thereof. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include the actual timing and content of submissions to and decisions made by the EU, US and Japanese regulatory authorities regarding the marketing authorization applications for Myozyme, Genzyme's ability to obtain labeling approval of Myozyme for treatment of all Pompe patients on infantile-onset clinical trial data, the timely receipt of pricing and reimbursement approvals in approved countries, the ability to manufacture sufficient quantities of product for development and commercialization activities and to do so in a timely and cost efficient manner, and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission. Please see the disclosure under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Quarterly Report on Form 10-Q for the period ended March 31, 2005 for a more complete discussion of these and other risks. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements. Genzyme® and Myozyme® are registered trademarks of Genzyme Corporation. All rights reserved. Genzyme Reports Interim Results from Pivotal Study of Myozyme CAMBRIDGE, Mass.—Genzyme Corp. (Nasdaq: GENZ) announced today that it has completed a planned analysis of interim data from its pivotal clinical trial of Myozyme® (alglucosidase alfa), which is being studied for the treatment of Pompe disease. The interim analysis was included in the trial’s protocol to allow for the potential expedited submission of a biologics license application. It found that the trial has already met one of its key secondary efficacy endpoints and that there is a high probability the study will meet its primary efficacy endpoint upon completion "The results are extremely encouraging and confirm our plan to submit a BLA in the middle of this year," said Richard A. Moscicki, senior vice president and chief medical officer for Genzyme Corp. "This analysis will allow us to seek U.S. approval for Myozyme as quickly as we had expected and to supplement our previously filed European marketing application with data from the pivotal study. We have proceeded with a great sense of urgency throughout the development of Myozyme, given the devastating nature of Pompe disease." The pivotal trial, known as AGLU01602, includes 18 patients with infantile-onset Pompe disease. These patients were enrolled in the trial and began receiving Myozyme by 6 months of age. Because of the rapidly progressive and fatal nature of infantile-onset Pompe disease, outcomes for these patients are being compared with a matched historical cohort rather than a placebo cohort. The study’s primary endpoint is the proportion of patients treated with Myozyme who are alive and free of invasive ventilator support at 18 months of age, compared with the proportion of patients who were alive at 18 months of age in the historical cohort (2 percent). Results for the primary endpoint will be known this summer, when patients will have completed 52 weeks of treatment. By 12 months of age, 89 percent of patients treated with Myozyme (16 of 18) were alive and free of invasive ventilator support compared with 17 percent of patients who were alive at 12 months of age in the historical cohort. This result meets a secondary efficacy endpoint and indicates the trial will very likely meet its primary endpoint. The interim analysis also found the following:
Genzyme will submit data from study AGLU01602 to the European Medicines Agency, which is reviewing a marketing authorization application (MAA) for Myozyme filed in December 2004. The agency’s Committee for Human Medicinal Products is expected to make a decision on the application later this year. The MAA contains data from other studies, including AGLU01702, which enrolled patients with infantile-onset Pompe disease who were older than those in AGLU01602 and whose disease was more advanced. Genzyme is pursuing approval for Myozyme’s use as a long-term enzyme replacement therapy for all patients with a confirmed diagnosis of Pompe disease, defined as acid alpha-glucosidase deficiency. There is currently no approved treatment for the disease. More than 100 patients are now receiving Myozyme in clinical studies, through Genzyme’s expanded access program, or through pre-approval mechanisms sponsored by governments in several European countries. The Myozyme program is Genzyme’s largest research and development initiative. About Pompe disease Pompe disease is an inherited, progressive muscle disease that affects fewer than 10,000 people worldwide. The disease is caused by a deficiency of an enzyme known as acid alpha-glucosidase. This deficiency leads to the excessive accumulation of glycogen in the body, particularly in the muscles. Pompe disease manifests as a broad spectrum of clinical symptoms with varying rates of disease progression. Infantile-onset patients present in the first months of life with an enlarged heart and skeletal and respiratory muscles weakness, and most die from cardiac or respiratory complications by one year of age. Late-onset patients may present with muscle or respiratory weakness anytime during childhood or adulthood, and disease progression is less rapid. Late-onset patients often require mechanical ventilation for breathing assistance and mobility aids such as canes, walkers or wheelchairs. Late-onset patients will experience a shortened lifespan due to progressive respiratory failure. Pompe disease belongs to a family of approximately 40 rare inherited diseases known as lysosomal storage disorders. About Genzyme One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Founded in 1981, Genzyme has grown from a small start-up to a diversified enterprise with annual revenues exceeding $2 billion and more than 7,000 employees in locations spanning the globe. With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields as well as heart disease and other areas of unmet medical need. This press release contains forward-looking statements, including statements about clinical trial results, regulatory plans and expected timelines for Myozyme, including the completion of the AGLU-01602 trial and the timing thereof, the submission of a BLA to the FDA and the timing thereof, and the expected timing of a decision from the Committee for Human Medicinal Products on Genzyme’s MAA. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: the actual timing and content of submissions to and decisions made by the US and EU regulatory authorities regarding marketing authorization applications for Myozyme; the actual timing and final results of the Myozyme clinical trials; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission. Please see the disclosure under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Annual Report on Form 10-K for the year ended December 31, 2004 for a more complete discussion of these and other risks. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements. Genzyme® and Myozyme® are registered trademarks of Genzyme Corporation. All rights reserved. Media Contact Investor Contact Genzyme Files for European Approval of Myozyme® For Treatment of Pompe Disease Media Contact: Investor Contact: CAMBRIDGE, MA—Genzyme Corp. (Nasdaq: GENZ) announced today that the European Medicines Agency (EMEA) has accepted its marketing authorization application for Myozyme® (alglucosidase alfa), an investigational enzyme replacement therapy for Pompe disease. If approved, Myozyme would become the first treatment available to patients with Pompe disease, a debilitating and often fatal muscle disorder resulting from an inherited enzyme deficiency. The EMEA’s Committee for Human Medicinal Products is expected to issue an opinion on the Myozyme application within one year, and a decision by the European Commission is anticipated early in 2006. “Pompe disease takes a devastating toll on patients and their families,” said Henri A. Termeer, chairman and chief executive officer of Genzyme. “We have proceeded with a great sense of urgency to develop a product that we hope and believe will finally give them a chance. We are enormously grateful to everyone who has contributed so much to get us to this point, and we are working diligently to begin the approval process for Myozyme in other parts of the world next year.” Myozyme has received orphan medicinal product designation, which applies to treatments for diseases that affect fewer than 5 in 10,000 people in the European Union. Approved orphan medicinal products are granted market exclusivity for 10 years. Genzyme is seeking approval for Myozyme’s use as a long-term enzyme replacement therapy for all patients with a confirmed diagnosis of Pompe disease, defined as alpha-glucosidase deficiency. Genzyme’s marketing application for Myozyme contains results from several clinical trials, including interim data from the ongoing study AGLU-01702, which is evaluating the use of Myozyme in severely affected children between 6 months and 3 years of age. One-year results from AGLU-01702 will become available during the application-review process, as will interim data from the ongoing study AGLU-01602, which is fully enrolled and includes children younger than 6 months of age with the classical infantile-onset form of Pompe disease. Nearly 100 Pompe patients are currently receiving Myozyme in clinical studies, through Genzyme’s expanded access program, or through pre-approval access mechanisms sponsored by governments in several European countries. “This is a very hopeful moment for people with Pompe disease in Europe,” said Ria Broekgaarden, of the Dutch Pompe patient organization VSN (Vereniging Spierziekten Nederland) and secretary of the International Pompe Association. “Patients urgently need treatment, and we will continue to advocate on their behalf.” Genzyme anticipates submitting a marketing application for Myozyme in the United States in the middle of 2005. Applications in Japan and other countries will follow the U.S. submission. The company continues to make a significant investment in the development of Myozyme, which is its largest research and development project. Genzyme is currently conducting an observational study for patients with the late-onset form of Pompe disease and plans to initiate a placebo-controlled treatment study for late-onset patients next year. The company has also established a registry designed to improve knowledge about Pompe disease by documenting the natural course of the disease, disease management approaches and clinical outcomes. All patients are eligible to participate in the registry through their treating physicians. Genzyme is also engaged in a substantial expansion of manufacturing capacity for Myozyme at its facilities in both the United States and Europe. About Pompe disease Pompe disease is an inherited muscle disease that affects fewer than 10,000 people worldwide. The disease is caused by a deficiency of an enzyme known as acid alpha-glucosidase. This deficiency leads to the excessive accumulation of glycogen in the body, particularly in the muscles. Pompe disease manifests as a broad spectrum of clinical symptoms with varying rates of disease progression. Infantile-onset patients present in the first months of life with an enlarged heart and skeletal and respiratory muscle weakness, and most die from cardiac or respiratory complications by one year of age. Late-onset patients may present with muscle or respiratory weakness anytime during childhood or adulthood, and disease progression is less rapid. Late-onset patients often require mechanical ventilation for breathing assistance and mobility aids such as canes, walkers or wheelchairs. Late-onset patients will experience a shortened lifespan due to progressive respiratory failure. Pompe disease belongs to a family of approximately 40 rare inherited diseases known as lysosomal storage disorders. About Genzyme Genzyme Corporation is a global biotechnology company dedicated to making a major positive impact on the lives of people with serious diseases. The company's broad product portfolio is focused on rare genetic disorders, renal disease, osteoarthritis and immune-mediated diseases, and includes an industry-leading array of diagnostic products and services, and sophisticated biomaterials. Genzyme's commitment to innovation continues today with research into novel approaches to cancer, heart disease, and other areas of unmet medical need. Approximately 7,000 Genzyme employees in offices around the globe serve patients in more than 80 countries. Safe-Harbor Statement This press release contains forward-looking statements, including statements about: the potential receipt of marketing approval for Myozyme in Europe; regulatory plans and expected timelines, including without limitation the expected timing of an opinion from the Committee for Human Medicinal Products and a decision from the European Commission; the expected timing of regulatory submissions in the United States, Japan and other countries; clinical trial plans; and estimates concerning the Pompe patient population. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: the actual timing and content of submissions to and decisions made by the Committee for Human Medicinal Products, the European Commission and other regulatory authorities regarding marketing authorization applications for Myozyme and the labeling for Myozyme; the actual timing and results of clinical trials of Myozyme; the ability to manufacture sufficient quantities of product for development and commercialization activities and to do so in a timely and cost efficient manner; the accuracy of the company’s information about the Pompe patient population; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission. Please see the disclosure under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme's Quarterly Report on Form 10-Q for the quarter ended September 30, 2004 for a more complete discussion of these and other risks. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements. Genzyme® and Myozyme® are registered trademarks of Genzyme Corporation. All rights reserved. July 2003 Enrollment has begun for a new clinical trial designed to treat patients with infantile onset Pompe disease. This protocol is open at Duke University Medical Center in Durham, North Carolina, USA. For more information contact.
Details about the
treatment study design are posted on the internet at: Genzyme Begins Enrolling Patients in Pivotal Pompe Disease Study Genzyme General (Nasdaq: GENZ), a division of Genzyme Corp., announced today that it has treated the first patient in a pivotal clinical trial evaluating the use of its MyozymeTM recombinant human acid alpha-glucosidase enzyme (rhGAA) as a potential treatment for Pompe disease. The trial, study 1602, is the second clinical trial that Genzyme initiated with this treatment this year, and will include up to 16 infants younger than six months of age at the time of their first infusion. Genzyme began enrollment in March of a clinical trial of Myozyme (study 1702) focused on children between the ages of six months and three years. Genzyme expects to complete enrollment in both studies this year and to apply for marketing approvals for Myozyme in 2004 based on results from these trials, and on previous studies of enzyme replacement therapy for Pompe disease. Both studies involve patients with the infantile-onset form of Pompe disease, in which symptoms manifest themselves during the first year of life. The 1602 trial announced today will examine the effect that Myozyme has at different doses on patient survival and on clinical factors such as respiratory function, and cardiac and muscle function. Infants with the most severe form of Pompe disease rarely survive more than one year without treatment. By contrast, the patients enrolled in the 1702 study announced in March span a broader range of symptoms and severity. Genzyme intends to use the results of these two trials to support global product registrations of Myozyme. "The start of this clinical trial marks another important step toward the development of a safe and effective treatment for children with this devastating disorder," said Richard Moscicki, MD, Genzyme's chief medical officer and senior vice president of medical, clinical, and regulatory affairs. "We are enormously conscious that for these children, time is of the essence. We are continuing to work diligently with our clinical investigators and regulatory authorities to bring this important therapy to patients as quickly as possible." Both studies initiated this year are multi-center, international trials involving treatment sites in the United States and Europe. The 1602 study will also include a treatment site in Taiwan, where the disease is more prevalent. About Pompe Disease Pompe disease is a rare and sometimes fatal muscle disease caused by an inherited deficiency of the enzyme acid alpha-glucosidase (GAA), which is responsible for breaking down glycogen within specialized compartments called lysosomes in cells. Pompe disease ranges from a rapidly fatal infantile-onset form with severe cardiac involvement to a more slowly progressive late-onset form primarily affecting skeletal muscle. There is currently no therapeutic treatment available for the disease, which affects an estimated several thousand people worldwide. Genzyme General develops and markets therapeutic products and diagnostic products and services. Genzyme General has six therapeutic products on the market and a strong pipeline of therapeutic products in development focused on the treatment of genetic diseases and other chronic debilitating disorders with well-defined patient populations. Genzyme General is a division of Genzyme Corp. This press release contains forward-looking statements, including statements about: plans concerning clinical trials for a potential therapy for Pompe disease, including the anticipated timing and design of trials; estimates concerning the Pompe patient population; plans regarding submissions to regulatory authorities; and the potential future availability of a therapy for Pompe disease. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: the receipt of IRB approvals for clinical trials and the timing thereof; enrollment rates for clinical trials; the actual efficacy and safety of rhGAA in humans and the actual timing of clinical trials; the results of pre-clinical and clinical studies; the actual timing and content of submissions to and decisions made by regulatory authorities concerning the Pompe product candidate and facilities, including the nature and extent of data required for marketing applications; the results and timing of qualifying runs at facilities; the ability to manufacture sufficient quantities of product for development activities (including without limitation extension studies and expanded access arrangements) and to do so in a timely and cost-efficient manner; the accuracy of Genzyme's information concerning the Pompe patient population; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation Exhibit 99.2 to Genzyme's 2002 Annual Report on Form 10-K, as amended. Genzyme General Division common stock is a series of common stock of Genzyme Corporation. Therefore, holders of Genzyme General Division common stock are subject to all of the risks and uncertainties described in the those reports. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and we undertake no obligation to update or revise the statements. Genzyme General Begins Enrolling Patients in Pompe Disease Study CAMBRIDGE, Mass – Genzyme General (Nasdaq: GENZ), a division of Genzyme Corp., announced today that it has begun enrolment in a clinical trial evaluating the use of its Myozyme™ recombinant human acid alpha -Glucosidase enzyme as a potential treatment for Pompe disease. The trial is the first of two studies Genzyme expects to conduct this year involving patients with the infantile-onset form of Pompe disease, in which symptoms manifest themselves during the first year of life. The trial (known as study 1702) will include up to 16 children between the ages of six months and three years. It is being conducted at medical centers in the United States and Europe. A second trial (known as study 1602) is scheduled to begin this spring, and will include up to 16 infants younger than six months of age at the time of their first infusion. Genzyme expects to complete enrolment in both studies this year. The studies will focus on the effect of Myozyme on patient survival, as well as other factors such as respiratory function, cardiac status, motor development, and safety. Genzyme expects to pursue product registrations globally based on results from these trials and previous studies of enzyme replacement therapy for Pompe disease. "We are moving forward with sense of urgency to complete these studies,” said Henri A. Termeer, chairman and chief executive officer of Genzyme Corp. “This is a devastating disease, and we are committed to doing all that is necessary to bring forward a safe and effective treatment for patients.” About Pompe disease Pompe disease is a rare and fatal genetic disorder caused by a deficiency of the lysosomal enzyme acid alpha- Glucosidase, which is responsible for breaking down glycogen within cells. Pompe disease shares a common element of muscle wasting with more than 40 different muscle diseases, often called muscular dystrophies. There is currently no treatment available for this disease, which affects several thousand people worldwide. Pompe disease ranges from a rapidly fatal infantile-onset form with severe cardiac involvement to a more slowly progressive adult-onset form. Genzyme General develops and markets therapeutic products and diagnostic products and services. Genzyme General has five therapeutic products on the market and a strong pipeline of therapeutic products in development focused on the treatment of genetic diseases and other chronic debilitating disorders with well-defined patient populations. Genzyme General is a division of Genzyme Corp. This press release contains forward-looking statements, including statements about: planned clinical trials for a potential therapy for Pompe disease, including the anticipated timing and design of trials; plans regarding submissions to regulatory authorities; and manufacturing plans and expectations. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: the receipt of IRB approvals for clinical trials and the timing thereof; enrolment rates for clinical trials; the efficacy and safety of Genzyme rhGAA in humans and the actual timing and final design of clinical trials; the results of pre-clinical and clinical studies; the actual timing and content of submissions to and decisions made by regulatory authorities concerning the Pompe product candidate and facilities, including the nature and extent of data required for marketing applications; the results and timing of qualifying runs at facilities; the ability to manufacture sufficient quantities of product for development activities (including without limitation extension studies and expanded access arrangements) and to do so in a timely and cost-efficient manner; and the risks and uncertainties described in reports filed by Genzyme 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. Genzyme General Division common stock is a series of common stock of Genzyme Corporation. Therefore, holders of Genzyme General Division common stock are subject to all of the risks and uncertainties described in the those reports. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and we undertake no obligation to update or revise the statements. Genzyme® is a registered trademark of Genzyme Corporation. All rights reserved. Transgenic Enzyme Production to CeaseIn July 2002, Genzyme began the transition of the nine transgenic (rabbit derived enzyme) patients to the CHO derived product. Three of the nine patients (infantile patients in the Netherlands) will remain on the transgenic enzyme until April 2003, when supply will be depleted. Genzyme General Reports 33 Percent Increase In Third-Quarter RevenuesOctober 18, 2001 This is an extract from the full press release. the interesting thing to note is the $17.2 Million set aside to ensure continued production of the transgenic enzyme for those patients who need it. CAMBRIDGE, Mass.-Genzyme Corp. today announced third-quarter financial results for Genzyme General (Nasdaq: GENZ). Revenues for the quarter were $255.1 million, 33 percent greater than revenues of $192.2 million for the same quarter last year. Profit before special items and amortization was $64.1 million, or $0.30 per diluted share, up 16 percent from $55.2 million, or $.30 per diluted share, in the third quarter of last year. Profit before special items and amortization was calculated this quarter using approximately 217 million diluted shares, compared to 194 million diluted shares in the third quarter last year. This year-to-year increase reflects the issuance of new shares for the acquisition of GelTex Pharmaceuticals Inc. in December 2000 and additional shares from exercised options. Including the shares related to the acquisition of Novazyme Pharmaceuticals Inc., Genzyme expects to conclude the year with approximately 220 million shares outstanding. Genzyme General recorded a number of special items in the quarter related to its ongoing commitment to develop a treatment for Pompe disease. First, it recorded a charge of $86.8 million for in-process research and development associated with the Novazyme acquisition. In addition-as a result of the decision by Pharming Group N.V. to file for receivership-Genzyme created a $17.2 million reserve to fund the continued production of transgenic enzyme for nine patients with Pompe disease participating in the extension of a clinical trial formerly sponsored by Genzyme and Pharming. Genzyme also wrote down $14.9 million in amounts owed by Pharming to Genzyme. Genzyme Acts to Ensure Continued Treatment of Pompe Patients (On Transgenic Enzyme) August 23, 2001 CAMBRIDGE, Mass—Genzyme Corp. announced today that it will fund production of the transgenic enzyme being used to treat nine patients with Pompe disease until they can be transitioned to a form of the enzyme derived from CHO cells, as planned. Genzyme took this action following the decision by its partner Pharming Group N.V. to file for receivership. Genzyme has asked for a commitment from Pharming to continue to produce the enzyme and to supply it to the hospitals involved in the treatment of these patients. The transgenic enzyme is manufactured by Pharming, and under a joint venture agreement, Genzyme and Pharming had shared production costs equally. The nine patients previously took part in clinical trials sponsored by the companies and have remained on therapy following the conclusion of those trials. “The welfare of the patients currently undergoing enzyme replacement therapy with the transgenic product is of utmost concern to Genzyme,” said Jan van Heek, executive vice president of Genzyme Corp. Mr. van Heek added that once Genzyme recently became aware of Pharming’s financial situation, it initiated exhaustive discussions with the company to propose a solution that was in the best interests of patients. Genzyme’s offer to acquire Pharming’s 50 percent interest in the two joint ventures the companies formed to develop a treatment for Pompe disease was not accepted by Pharming’s board of directors. Discussions continue to resolve matters related to the joint ventures. Genzyme and Pharming began working in partnership in 1998. The companies jointly sponsored clinical studies of transgenic human alpha-Glucosidase at the Sophia Children’s Hospital in Rotterdam, The Netherlands, and similar studies at the University Hospital of Essen, Germany. In April 2000, the companies switched the focus of their development efforts to a form of human alpha-Glucosidase derived from CHO cells. A Phase 2 clinical trial of this product is currently underway at medical centers in Europe and the United States. Given the seriousness of Pharming’s present financial situation and the need to move forward quickly with the development of a treatment for Pompe patients, Genzyme believes it has no choice but to take over full operational and financial responsibility for the development of the CHO-cell product. As a result, Genzyme today terminated its CHO-cell joint venture agreement with Pharming in accordance with the agreement’s provisions, based on Pharming’s failure to make ongoing payments to fund the program. The joint venture for the transgenic product remains in place. “Dealings with Pharming and its trustees have led us to conclude that assuming full responsibility for the program is the only choice to protect and advance the interests of Pompe patients,” said Mr. van Heek. “Pharming and its trustees need to focus on the survival and financial restructuring of Pharming. We need to devote our full attention to the needs of Pompe patients.” Genzyme is committed to developing an approved treatment for patients with Pompe disease around the world, and will continue to work diligently toward reaching that goal. The company recently announced its intention to acquire Novazyme Pharmaceuticals Inc., whose lead product candidate is NZ-1001, an enzyme replacement therapy for Pompe disease that is on track to enter clinical trials in the very near future. Genzyme will move forward aggressively with the development of NZ-1001, while it simultaneously completes the ongoing Phase 2 clinical trial of the CHO-cell-derived enzyme replacement therapy. Over the course of their three-year partnership, Genzyme has taken steps to provide support to Pharming. Genzyme was an early investor in the company. In addition, to help fund Pharming’s portion of the initial licensing payment for the CHO-cell product, Genzyme provided Pharming with a loan of $10 million in exchange for a convertible note. Genzyme Corporation is a U.S. based biotechnology company that develops and markets products and services designed to address unmet medical needs. Genzyme’s European headquarters is located in Naarden, The Netherlands. This press release contains forward-looking statements, including statements about: Genzyme’s plans with respect to the transgenic enzyme product and other potential therapies for Pompe disease; the anticipated acquisition of Novazyme; the potential development of products using Novazyme’s technology and potential indications thereof; and plans concerning clinical trials. Actual results may materially differ due to numerous factors, including without limitation: Pharming’s ability to continue production of the transgenic enzyme and to do so without interruption, in a timely manner and in sufficient quantities; conditions in the financial markets relevant to the proposed acquisition; the satisfaction of the conditions to closing the proposed acquisition; the risks generally associated with acquisitions; the actual timing and results of pre-clinical and clinical studies; the efficacy and safety of products; the content and timing of submissions to and decisions by regulatory authorities; and the risks and uncertainties described in Genzyme’s reports filed with the U.S. Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation Exhibit 99.2 to Genzyme’s Annual Report on Form 10-K for the year ended December 31, 2000, as amended. Media Contact: Bo Piela--Tel: 1-617-252-7785 Pharming Pharming B.V. Excerpts from Pharming Press Release Leiden, the Netherlands, 1 August 2000 - Pharming Group N.V. Pharming strengthened partnership with Genzyme
Product Development Human alpha-Glucosidase: Pompe's disease In April, Pharming and Genzyme announced their intention to co-develop and commercialize Pompase® enzyme replacement therapy for Pompe's disease; a therapy based on human alpha-Glucosidase (hAG) produced in CHO-cells. Genzyme had acquired the exclusive rights to Pompase® from Synpac, Inc., and had offered these rights to the Pharming/Genzyme joint venture. Pharming has issued a convertible note of USD 10 million to Genzyme as part of this acquisition. By focusing on CHO-cells for the production of hAG, Pharming and Genzyme have ensured that in the end, a therapy for Pompe's disease will come available in the shortest possible time. Final agreement was reached June 30, 2000. All patients currently in clinical trials in both Rotterdam, the Netherlands and Essen, Germany are doing relatively well and will continue to receive transgenically produced hAG until a transition to CHO-material is deemed feasible and acceptable. At present, clinical data for both the transgenic product and the CHO-product are being compared . The prospective clinical trial in severe infantile Pompe patients will start in the second half of 2000. These infantile patients will be treated with CHO derived hAG in the US and Europe, and will be compared to a historical control group. The trial is expected to last for 12 months, with market launch expected in 2002. A prospective juvenile trial will start in 2001, and will be expected to complete in 2003. The construction of the multi-purpose plant in Geel, Belgium will be completed as planned. With the shift to CHO-cells for the production of hAG, the extra available capacity will benefit the other development programs. Results of first 36 weeks of treatment in infants published in The Lancet July 29, 2000 Recombinant human
alpha-glucosidase from rabbit milk in Pompe patients Following is a short summary of the information published: The results of the effects of the enzyme, human acid alpha-glucosidase, on four infantile Pompe patients was described by Ans Van der Ploeg, M.D, Ph.D., et al, in this issue of The Lancet Interactive. It documented the successful treatment of 4 babies with the infantile form of Pompe's disease who were treated with recombinant human alpha-glucosidase from the milk of transgenic rabbits. The results showed that there was uptake of the enzyme in skeletal muscle and the muscle function was stimulated. The treatment reduced heart size, improved heart function and condition, and seemed to be responsible for the prolonged lives of the four babies in the clinical trial. Pompe's disease is a fatal muscle disease caused by the lack or deficiency of the lysosomal enzyme acid alpha-glucosidase (acid maltase). The infantile form of the disease is usually fatal within the first year of life. All four babies in the trial passed this critical one year juncture. The report covered the first 36 weeks of the infantile clinical trial which began in January 1999, and is still ongoing in the Netherlands at Sophia Children's Hospital, an affiliate of Erasmus University, Rotterdam. Genzyme General April 20, 2000 Genzyme General
Obtains Rights to Pompe Disease Therapy from Synpac see press release April 20, 2000 Pharming Pharming B.V. Pharming's first Phase II clinical trial for Pompe's disease finalised, showing survival, skeletal muscle regeneration and overall improvement of heart and lung functions Leiden, the Netherlands, March 15, 2000 The bio-pharmaceutical company Pharming Group N.V. (Pharming) of Leiden, the Netherlands (AEX, EASDAQ: PHAR), in conjunction with its joint venture partner, Genzyme General of Cambridge, MA, USA (NASDAQ: GENZ) has finalized with positive results its first Phase II clinical study with transgenic recombinant human alpha-Glucosidase. The study was a single center open label Phase II study in infantile Pompe patients, performed at the Sophia Children's Hospital in Rotterdam, the Netherlands, with Dr Ans van der Ploeg, pediatrician and a world expert on Pompe's disease, as principal investigator. Pompe's disease is a hereditary, lethal muscle disorder, for which until now there has been no therapy. The human alpha-Glucosidase for the clinical trial in Rotterdam has been produced in the milk of Pharming's transgenic rabbits at its plant in Geel, Belgium. Normal levels After 36 weeks in the study, the four included infantile patients have reached the age range of 12 to 17 months, which is well beyond the mean age of survival in untreated infantile Pompe patients. Repeated muscle biopsies demonstrated that the transgenic recombinant enzyme is taken up by the main target tissue, skeletal muscle, reaching normal levels of alpha-Glucosidase activities, which are comparable to healthy individuals. In the skeletal muscle tissue, the enzyme shows to be active, since on histological evaluation, lysosomal glycogen storage decreased and muscle regeneration was observed. The most prominent effect was seen on the heart. In untreated patients, the left ventricular posterior wall thickness increases over time as the disease progresses. After start of treatment, the slope of left ventricular posterior wall thickness versus time changed significantly for all four patients, This was in-line with a concomitant significant decrease of left ventricular mass index (a measure for the dimension of the left ventricle) over time, with the largest improvement to less than 30% of the baseline value at the beginning of the study. In addition, symptoms of cardiac instability diminished in all patients, The treatment appears to have an effect on respiratory function. The two patients included prior to 3 months of age did not become dependent on artificial ventilation and currently they are treated as outpatients, receiving their weekly treatment on a day care basis. Objective The objective of this clinical study was to obtain data of safety and efficacy of alpha-Glucosidase. Following a two-week baseline period, four patients were included and treated for 36 weeks for a total of 144 infusions. Patients were started at a dose of 15 and 20 mg/kg per week while during the study, based or monitoring of muscle tissue activity levels, the dose was increased to 40 mg/kg in a once a week intravenous infusion. The enzyme was generally well tolerated, Adverse events reported were fever, malaise, erythematous rash, sweating, hypoxia, flushing and tachycardia. These events were transient and could be well managed. No changes were found in routine hematology and clinical chemistry and no changes in blood pressure during or after infusion were observed. Skeletal muscle function and strength improved in all patients, with one patient reaching development milestones which are beyond normal observations for untreated patients with infantile Pompe's disease. Generally the increase in muscle function was best observable in the strength of the arms. Long term follow-up will be needed to assess the final outcome: safety, efficacy and impact on quality of life for these children and their respective families. Critical breakthrough "Of course we will not draw final conclusions at this stage of our clinical studies, but the results so far have exceeded our initial expectations", says George J.M. Hersbach, president and chief executive officer of Pharming. "For myself, as president of this company, it is really moving and exciting at the same time to hear that one of the infants in the trial can even walk now without help of its parents. Pharming will supply the four children with its human alpha-Glucosidase to continue treatment. To stay alive, the children need life-long treatment." George Hersbach adds that the results in Rotterdam represent a critical breakthrough for Pharming, and the medical world as a whole. The study lends weight to the idea that using transgenic animals to produce critical human proteins is an effective way of combating some of the most difficult-to-treat illnesses," Filing beginning 2001 A few months ago a second Phase II clinical trial was started simultaneously by the same investigation team at the Sophia Children's Hospital in Rotterdam, in which three juvenile Pompe patients are involved, who are treated with Pharming's transgenic recombinant alpha-Glucosidase. The first results of that trial are expected to be available before this summer. A Phase 1 infantile clinical trial has been set up recently by the Pharming / Genzyme joint venture in Essen, Germany. With further positive results, regulatory filing for alpha- Glucosidase for the first treatment of Pompe's disease might be possible beginning of 2001 envisioning market launch mid 2001. In October 1998 Pharming and Genzyme formed a joint venture to develop enzyme replacement therapy for the lysosomal storage disorder Pompe's disease. Pharming focuses on the development, production, and worldwide commercialization of human therapeutic proteins, produced at high levels in the milk of transgenic animals that have been created using the company's proprietary technology. Human alpha-Glucosidase is the most developed of Pharming's products, and focuses on Pompe's disease, an 'orphan disease'...... Pharming Pharming B.V.
Following are excerpts from the Pharming Group
NV third quarter press release:
The following information was released at the fifteenth annual AGSD-UK Conference on October 9, 1999
PHARMING Medical Team Rotterdam (NL) Satisfied with Progress in Pompe Disease Phase II Clinical Trial with Human Alpha-Glucosidase Leiden, The Netherlands, June 1, 1999 – At a press conference and an analyst’s meeting held in Amsterdam today, Pharming Group N.V. (Easdaq: PHAR) presented an update on developments and programs of the company. Pharming has become one of the key biopharmaceutical companies in Europe. Worldwide it is nearing the top 60 of the biotechnology industry. Its principal clinical development program with human alpha-Glucosidase for Pompe’s disease is on schedule and shows favorable preliminary results. Pharming is also making substantial progress with its development programs for human Lactoferrin and human C1 Esterase inhibitor. The company’s patent portfolio expands continuously and now counts some 24 patents. Clinical trials: human
alpha-Glucosidase Pharming’s place in the
European Life Sciences Industry Clinical development programs:
human Lactoferrin and human C1 Esterase inhibitor The US Food and Drug Administration has granted Pharming orphan drug designations for its product recombinant human C1 Esterase inhibitor, in both prophylaxis and acute treatment of hereditary and acquired angioedema (HAE). The number of patients in the western world suffering from HAE is estimated to be between 10,000 and 50,000. Pharming has succeeded in producing human C1 Esterase inhibitor in the milk of transgenic rabbits and is currently setting up the necessary purification facilities. Expanding the patent portfolio Development programs Pharming focuses on the development, production and worldwide commercialization of human therapeutic proteins, produced at high levels in the milk of transgenic animals that have been generated using the Pharming’s proprietary technology. Excerpts
from......... Phase II Clinical Trial for Pompe's Disease on Track Leiden, The Netherlands,
May 3, 1999 - Pharming Group N.V. Product Development Patents Corporate Affairs "Pharming has had a strong start to the year, and our lead program, the Phase II clinical trial with human alpha-Glucosidase for Pompe's disease, progressing well," said George J. M. Hersbach, President and Chief Executive Officer of Pharming Group N.V. "We also received our second Orphan Drug Designation for human C1 Esterase inhibitor, which is very good news for our product development portfolio and testimony to the excellent performance of our Orphan Products business unit. Pharming has a very strong cash position that will allow us to support the market launch of human alpha-Glucosidase, and to further develop our product portfolio." Pharming focuses on the development, production and world-wide commercialization of human therapeutic proteins, produced at high levels in the milk of transgenic animals that have been generated using the Pharming's proprietary technology. Phase II Pilot
Trials Begin (January 1999) in the Netherlands Following is background information and a Q & A released by the Pharming/Genzyme LLC on important issues concerning clinical trials for enzyme replacement therapy now underway in the Netherlands on acid maltase deficiency, Pompe's disease. Background--Pompe Disease Pompe disease is one of a family of 40 rare diseases known as lysosomal storage disorders. Pompe disease, also known as acid maltase deficiency or glycogen storage disease type II, is caused by complete or partial deficiency of the enzyme alpha -glucosidase and affects an estimated 5,000-1 0,000 people in the Western world. Another well-known example of a lysosomal storage disorder is Gaucher disease, which is caused by deficiency of the enzyme glucocerebrosidase. For Gaucher disease, there is an existing enzyme replacement therapy, in fact the first such therapy for a lysosomal storage disorder. Clinical forms of Pompe disease vary according to the age of onset and progression of symptoms. The infantile form appears in the first few months after birth and is characterized by a rapid build-up of glycogen in several tissues, severe muscle weakness, and enlargement of the heart and liver. Respiratory and heart complications often lead to an early death in the first or second year of life. 'The juvenile form usually begins in early childhood and develops more slowly. It is characterized by progressive muscle weakness, with the respiratory muscles being most critically affected. Patients with this form of the disease usually succumb to respiratory failure before the age of 30. In the adult form of the disease, symptoms may go undetected until the third to fifth decade of life. Glycogen build-up occurs mainly in skeletal muscle, leading to muscular weakness, particularly in the diaphragm, limb girdle and the trunk. Respiratory complications are the main cause of death. Alpha-glucosidase production Pharming has pioneered the production of recombinant human proteins isolated from the milk of transgenic animals. This technology allows for efficient production of complex proteins which may be difficult to produce (technically or economically) by other methods. In the particular case of Pompe disease, Pharming has succeeded in producing the enzyme human alpha-glucosidase at high levels in the milk of transgenic rabbits. The production of human alpha-glucosidase currently takes place at Pharming's small scale pilot plant in Geel, Belgium. The pilot plant is capable of producing sufficient alpha-glucosidase for clinical trials. In addition, Pharming is constructing a commercial scale plant for commercial production of the enzyme after product approval. The plant's completion is expected in the year 2000. In October 1998, a joint venture was established between Pharming Group, N.V. of the Netherlands and Genzyme Corporation, of Cambridge, Massachusetts for the worldwide development and commercialization of human alpha-glucosidase (the joint venture). The first steps of human alpha-glucosidase development The safety and efficacy studies for alpha-glucosidase in animals were concluded with positive results. The study showed that regular intravenous injection of the recombinant human alpha-glucosidase appeared to correct the enzyme deficiency and significantly improve tissue morphology with generally few side effects. Pharming then proceeded to take human alpha-glucosidase into Phase I clinical trials to test the safety and tolerance of the enzyme in human subjects. Participants in this trial were healthy (adult) volunteers. The study was concluded in the summer of 1998 with encouraging results: human alpha-glucosidase was generally safe and well-tolerated. It is important to note that these are preliminary results. More studies in patients are needed to confirm these findings before an application seeking marketing approval can be submitted to the Regulatory Authorities. Human alpha-glucosidase in Phase II clinical trials and beyond As a first step to test recombinant human alpha-glucosidase in Pompe disease patients, a pilot trial will be carried out at Sophia Children's Hospital in Rotterdam, under the direction of Pharming/Genzyme LLC. The aim of the study is to assess for the first time the safety and early indications of efficacy of the enzyme in patients. It will be a pilot trial with a limited number of infantile (approximately four) and juvenile patients (approximately three). Dr. Ans van der Ploeg at the Sophia Children's Hospital in Rotterdam is the principal investigator of the current pilot trial. Data obtained while the pilot study is in progress will be used to design two larger Phase II/III pivotal trials in the US and Europe. Detailed design of these trials can only be done when data from the pilot trial are available. The goal is to have these studies underway in mid1999. A relatively limited number of patients will be enrolled in the combined trials which is in line with the limited number of Pompe disease patients overall. It is also due to the fact that Pharming's pilot plant is not equipped to supply more human alpha-glucosidase than the scheduled trials demand, However, as a testimony of the Pharming/Genzyme LLC's conviction to the success of these trials, the company is currently constructing a commercial scale plant. Therefore, larger amounts will become available, as market demand increases. Questions and Answers 1. Have the clinical trials started? Approval for a small pilot study on 4 infants and 3 juvenile patients was recently received in the Netherlands. The study has begun (January 1999) at the Sophia Children's Hospital in Rotterdam and inclusion of patients has started. Dr. Ans van der Ploeg is the principal investigator. This study is designed to assess safety and give indications of efficacy of recombinant |