ERT Information



Editor's Note: Only responses from families of MPS and important press releases are posted here. All medical expert responses are posted on the Medical Expert Page. Last updated: March 21, 2001.


Editor's Note:This is an excerpt from a press release from Genzyme dated February 16, 2001.

Genzyme and joint venture partner BioMarin Pharmaceutical Inc. are actively enrolling MPS I patients in the pivotal Phase 3 trial of Aldurazyme? (laronidase) enzyme replacement therapy. Enrollment in the six-month trial is expected to conclude by the end of the first quarter, and Genzyme and BioMarin anticipate filing for U.S. marketing approval by the end of this year. Approval is anticipated by mid-2002.



Genzyme and Biomarin Announce Phase 3 Trial of Aldurazyme™ for MPS-I

Date: November 22, 2000

Genzyme General (Nasdaq: GENZ) and BioMarin Pharmaceutical Inc. (Nasdaq and Swiss SWX New Market: BMRN) announced on November 22 that they are initiating a pivotal Phase 3 trial of Aldurazyme™ (laronidase), and expect to treat the first patient in the trial by early December. The product, recombinant alpha-L-iduronidase, is an enzyme replacement therapy for patients with MPS-I, also known as Hurler, Hurler-Scheie and Scheie diseases. Genzyme and BioMarin have received Orphan Drug designation and Fast-Track status for Aldurazyme from the U.S. Food and Drug Administration. In an initial clinical trial, Aldurazyme has shown safety and promising clinical results. If the Phase 3 trial confirms the initial safety and efficacy profile of the drug, the companies will submit for marketing approval in the U.S., Europe, Canada and other countries in order to provide Aldurazyme therapy to the thousands of patients who currently suffer from this life-threatening disease. In 1998, Genzyme and BioMarin formed BioMarin/Genzyme LLC to develop and commercialize Aldurazyme throughout the world. BioMarin specializes in the development and commercialization of therapeutic enzyme products. Since inception in 1997, BioMarin has applied its proprietary enzyme technology to develop products for lysosomal storage diseases and for the treatment of serious burns. Glyko, Inc., a BioMarin subsidiary, provides analytical and diagnostic products and services in the area of carbohydrate biology. Genzyme General develops and markets therapeutic products and diagnostic products and services. Genzyme General has three therapeutic products on the products in development focused on the treatment of genetic disorders. Genzyme General is a division of the biotechnology company Genzyme Corporation. This press release contains forward-looking statements, including statements regarding: the expected timing of dosing patients in a Phase 3 trial; the clinical potential of Aldurazyme; anticipated submissions for regulatory approvals of Aldurazyme™ in the U.S. and Europe; and the potential market introduction of Aldurazyme. Actual results may differ materially from those contained in these forward-looking statements as a result of a number of factors, including: the actual safety and efficacy of Aldurazyme; the enrollment rates for the Phase 3 clinical trial; the results of clinical trials; the ability to manufacture sufficient amounts of Aldurazyme for development and commercialization activities; the timing and content of submissions to and decisions made by the FDA, the European Agency for the Evaluation of Medicine Products and other regulatory authorities; the continued funding of the joint venture; decisions made by physicians and third-party payers regarding the use of, and reimbursement for, Aldurazyme; our ability to obtain and maintain adequate patent and other proprietary rights protection for Aldurazyme; the scope, validity and enforceability of patents and other proprietary rights held by third parties related to therapies for MPS-1 and the actual impact of such patents and other rights on our ability to commercialize Aldurazyme; the competitive environment for therapies for MPS-1; and the risks and uncertainties described in Genzyme’s and BioMarin’s reports filed with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including Exhibit 99.2 to Genzyme’s Annual Report on Form 10-K for the year ended December 31, 1999, as amended. GENZ stock is a series of common stock of Genzyme Corporation. Therefore, holders of GENZ stock are subject to all of the risks and uncertainties described in the aforementioned reports filed by Genzyme Corporation.


Editor's Note:This is an excerpt from a press release from Genzyme dated April 20, 2000.

Genzyme General and its joint venture partner BioMarin Pharmaceutical Inc. continue to progress toward initiating the confirmatory phase III clinical trial of Aldurazyme enzyme replacement therapy for patients with MPS I. The companies expect to begin enrolling patients later this year. In preparation for the start of the trial, a decision was made by the joint venture to use BioMarin’s new Galli Drive facility in Novato, California, to manufacture Aldurazyme for the confirmatory trial, as this will be the same material used for commercial launch. Production of Aldurazyme at BioMarin’s Carson Street clinical manufacturing facility in Torrance, California, will be suspended at the end of this month



BioMarin and Genzyme to Conduct Confirmatory Trial of Treatment for MPS-I Prior to Filing for FDA Approval

Date: November 17, 1999

BioMarin Pharmaceutical Inc. (Nasdaq and Swiss SWX New Market: BMRN) and Genzyme General (Nasdaq: GENZ) today announced that they will conduct a confirmatory phase III clinical trial of Aldurazyme™enzyme replacement therapy for mucopolysaccharidosis-I (MPS-I) prior to seeking marketing approval from the FDA. Following a positive meeting with the FDA yesterday, the companies and the agency agreed to build on the encouraging results of the initial clinical trial of Aldurazyme with additional data supporting the therapeutic benefit of the product.

BioMarin and Genzyme now expect to file a biologics license application (BLA) for Aldurazyme in the United States by the end of next year, with market introduction coming in 2001. Regulatory filing in Europe will quickly follow the U.S. filing and will be based on results from the confirmatory phase III trial, which will involve centers in both the United States and Europe. The FDA confirmedthat Aldurazyme maintains its Fast-Track Status.

"MPS-I is a chronic, life-threatening disease, for which no effective treatment options exist. Since inception, the goal of BioMarin's program for Aldurazyme has been to expeditiously meet the needs of MPS-I patients," said Grant W. Denison, Jr., chairman and chief executive officer of BioMarin. "We are very pleased with the clinical results we've collected to date, which have exceeded the expectations we had when we began the trial. Building on that foundation, we will continue our work with the FDA on this confirmatory trial." Henri A. Termeer, chairman and chief executive officer of Genzyme Corporation, said: "Since we began this program, we have proceeded with a great sense of urgency, driven by our compassion for MPS-I patients. While today's decision extends the timing for the U.S. commercial launch of Aldurazyme, we expect that a confirmatory trial will strengthen our ability to transform the standard of care for MPS-I. By expanding the pool of available clinical data on Aldurazyme, we expect to accelerate acceptance of the product within the health care community. We are confident about Aldurazyme's potential, and we are working very closely with the FDA to make this product available as soon as possible."

In the initial clinical trial, Aldurazyme was administered on a weekly basis for 52 weeks to 10 patients with MPS-I ranging in age from 5 to 22 years. Patients met both of the primary endpoints prospectively defined in the clinical protocol. Specifically, patients experienced a normalization of liver size and showed a decrease in the excretion of urinary glycosaminoglycans, the carbohydrate substances that accumulate in patients with MPS-I. The patients who participated in the initial trial continue to receive treatment and are now approaching two years on therapy.

The confirmatory trial of Aldurazyme will be designed to collect additional data to supplement the positive results obtained in the initial clinical trial of the product. BioMarin and Genzyme are working with the FDA to finalize a protocol for the confirmatory trial. The companies expect trial enrollment to proceed quickly, given the number of MPS-I patients that they have identified through their physician and patient outreach. As in the initial trial of Aldurazyme, patients in the confirmatory trial are expected to represent the full spectrum of severity of MPS-I, including Hurler, Hurler-Scheie, and Scheie syndromes.

As part of the discussions with the FDA, the companies and the agency agreed that it is important to determine a protocol for treating the most severely ill MPS-I patients. BioMarin and Genzyme will work with the FDA to develop this protocol to allow early access to treatment for terminally ill patients. The data from this clinical study is not required for the BLA filing.

BioMarin and Genzyme General formed a joint venture in September 1998 for the development and commercialization of Aldurazyme for the treatment of MPS-I.

BioMarin Pharmaceutical Inc. specializes in the discovery, development and commercialization of carbohydrate enzyme therapeutics. Since inception in 1997, BioMarin has applied its proprietary enzyme technology to the development of products in five therapeutic areas: genetic diseases, burn debridement, fungal infections, male pro-fertility, and inflammation (psoriasis). Glyko, Inc., a BioMarin subsidiary, provides analytical and diagnostic services in the area of carbohydrate biology.

Genzyme General develops and markets therapeutic products and diagnostic products and services. Genzyme General currently has three therapeutic products on the market and a strong pipeline of therapeutic products in development focused on the treatment of rare genetic disorders. A division of the biotechnology company Genzyme Corporation, Genzyme General has its own common stock intended to reflect its value and track its economic performance.

This press release contains forward looking statements regarding our expectations for filing for the biologics license application and market introduction for Aldurazyme; the filing of a regulatory dossier in Europe for Aldurazyme; the locations of, and the protocol for, and the patient population for the confirmatory clinical trial of Aldurazyme; our ability to obtain a compassionate use protocol in that clinical trial; our ability to transform the standard of care for MPS-I; our ability to accelerate market acceptance for Aldurazyme; and the clinical potential of Aldurazyme. Actual results may differ materially from those contained in these forward looking statements as a result of a number of factors, including: the timing and content of submissions to and decisions made by the FDA, the European Commission and other regulatory authorities; enrollment rates and results of clinical trials; the ability to manufacture sufficient quantities of Aldurazyme for development and commercialization activities; the continued funding of the joint venture; decisions made by physicians and third party payers regarding the use of, and reimbursement for, Aldurazyme; and the actual clinical potential of Aldurazyme.

Aldurazyme™ is a trademark of BioMarin/Genzyme LLC. All rights reserved.



Genzyme and BioMarin Report that Patients in Pivotal Trial of a-L-iduronidase Show Marked Improvement

Data Presented at American Society of Human Genetics Meeting

CAMBRIDGE, Mass. and NOVATO, Calif., October 30, 1998.
MPS-I results from a genetic deficiency in the production of a -L-iduronidase, a key enzyme required for the progressive breakdown of complex carbohydrates found in all cells of the body. Data from the trial demonstrated that a -L-iduronidase replacement therapy reduced clinical measurements of the disease and improved patients’ ability to perform normal functions of daily life.

"The trial results are very encouraging," said Emil D. Kakkis, M.D., Ph.D., the study’s principal investigator, who presented the findings. "This clinical trial culminates 30 years of research and marks the first time enzyme replacement therapy has been used effectively with MPS-I patients." Dr. Kakkis is assistant professor, Division of Medical Genetics, Department of Pediatrics, Harbor-UCLA Medical Center. He also recently became president of BioMarin Genetics, a division of BioMarin Pharmaceutical.

Trial Design and Results

The clinical trial, which was initiated in December 1997 and conducted at the Harbor-UCLA Research and Education Institute in Torrance, California, in collaboration with four other leading medical centers, enrolled ten patients in a 26-week treatment protocol. MPS-I strikes children, with initial diagnosis typically at 2 or 3 years of age. The ages of those enrolled in the trial ranged from 5-22 years.

Patients were evaluated before the trial began to establish a clinical baseline. They were then given a weekly intravenous infusion of 125,000 units (~0.5mg) of a -L-iduronidase per kilogram of body weight. Patients were subsequently examined after weeks 6, 12 and 26. Both quantitative data and clinical/patient self-assessment data were collected and analyzed.

Quantitative MRI studies demonstrated that treatment with a -L-iduronidase was associated with a rapid 20 percent or more reduction in liver size after 6-12 weekly doses in nearly all patients, and that liver size returned to normal in the majority of patients by 26 weeks. Patients also showed a decrease in the excretion of urinary glycosaminoglycans, indicating the success of a -L-iduronidase in breaking down these complex carbohydrate materials, which otherwise will accumulate in patients with MPS-I. Urinary glycosaminoglycan levels typically dropped by the third or fourth dose of the enzyme, and all patients achieved a 60 percent or better reduction within 12 weeks.

In addition, patients reported improvements in physical abilities and quality of life. Joint pain was reduced and mobility improved, allowing patients to do more activities that had been difficult before, such as walk, run, swim, hang from monkey bars, or swing a bat. Patients also had substantial improvements in endurance and decreased fatigue. Difficulties in breathing were much improved and contributed to the improved endurance. For several patients, limited half days at school were extended to full days. The severe headaches with occasional vomiting that plagued some patients up to several times a week prior to treatment, were resolved after several weeks of therapy. Hearing and vision improved in certain patients.

Adverse events such as hives were noted in a minority of patients but were manageable and did not significantly affect the patients’ health. All patients who were enrolled in the trial continue to receive therapy and will be evaluated at 12 and 18 months following the initiation of treatment.

"From its inception, BioMarin has been dedicated to developing therapies which have the potential to change the practice of medicine and improve patients’ lives," said Grant W. Denison, Jr., chairman and chief executive officer of BioMarin. "Today’s trial results represent a step toward realizing that potential, showing that this treatment can have a major positive impact on the lives of MPS-I patients. We look forward to continuing the development of therapies which address unserved medical conditions."

Henri A. Termeer, chairman and chief executive officer of Genzyme Corp., said: "Genzyme has a deep commitment to helping patients with rare genetic disorders such as MPS-I. We are very excited by the potential this therapy has shown to improve patients’ lives. Through our joint venture with BioMarin, we will move forward immediately with our program to obtain regulatory approval for this treatment, which we hope to make available to patients very rapidly."

Genzyme and BioMarin Joint Venture

Alpha-L-iduronidase is being developed and commercialized through a joint venture of Genzyme and BioMarin. Genzyme and BioMarin expect to submit the data from this clinical trial in a Biologics License Application (BLA) for a -L-iduronidase, which the companies intend to file with the U.S. Food and Drug Administration (FDA) during the first quarter of 1999. The FDA has designated a -L-iduronidase a fast-track product. BioMarin received orphan drug designation for the enzyme in September 1997, giving the product market exclusivity for seven years following FDA approval.

Background on MPS-I MPS-I encompasses three syndromes—Hurler, Hurler-Scheie, and Scheie syndromes—that define ranges in a spectrum of severity. All types of MPS-I are caused by a deficiency in an active enzyme, a -L-iduronidase, which results in a build-up of carbohydrate materials called glycosaminoglycans in all tissues of the body. This build-up of stored material leads to cell, tissue and organ dysfunction. The debilitating effects of MPS-I lead to early death--often before the age of ten. Symptoms can include enlargement of the liver and spleen, joint pain and immobility, skeletal deformity, vision impairment, stunted growth, hearing loss, obstruction of airways, severe headaches and cardiomyopathy.

Approximately 2,000-3,000 patients in the developed world have been diagnosed with MPS-I. As with other lysosomal storage diseases, there are believed to be additional undiagnosed patients. There is currently no known effective treatment for MPS-I.

Genzyme General develops and markets therapeutic and surgical products and diagnostic products and services. A division of the biotechnology company Genzyme Corp., Genzyme General has its own common stock intended to reflect its value and track its performance.

BioMarin Pharmaceutical, Inc. is a privately held biopharmaceutical company specializing in the discovery, development and commercialization of carbohydrate enzyme therapeutics. Since inception in 1997, BioMarin has applied its proprietary enzyme technology to the development of products in five therapeutic areas: genetic diseases, burn and wound care, fungal infections, pro-fertility products and inflammation (psoriasis). With its recent acquisition of Glyko, Inc., BioMarin added analytical and diagnostic products and services in the area of carbohydrate biology.

This press release contains forward-looking statements about potential therapeutic uses of a-L-iduronidase, the potential market exclusivity of a-L-iduronidase, the size of the potential market for a-L-iduronidase, the ability of the current clinical trial of a-L-iduronidase to serve as a pivotal trial, and the expected filing dates for a BLA.

Results may differ materially depending on the therapeutic effect of a-L-iduronidase in commercial applications, the accuracy of information regarding the number of patients suffering from MPS-I, and decisions made by the FDA.

Genzyme’s releases are available at Genzyme and on the company’s fax-on-demand service at 1-800-436-1443 in the U.S. or 1-201-521-1080 elsewhere.



Editor's Note: This was copied with permission from the Holland family from the University of Minnesota's MPS Discussion Forum. With 3 children with Hurler Scheie Syndrome, they have vast experience with this disorder. Their oldest child, Spencer, had the chance to participate in the Enzyme Replacement Therapy.

Amy Holland (steve_amyholland@msn.com) February 12, 1999 (09:57)

Dear All,

Many parents have expressed an interest in Spencer's progress in regards to the clinical trial for ERT. If you are not familiar with our family, we have three children with hurler-scheie syndrome;Spencer(9), Maddie(7), and Laynie(5). Spencer began receiving enzyme treatments almost one year ago, as part of a clinical trial with Dr. Emil Kakkis. I take Spencer one day each week to a hospital that is an hour away and he receives an IV infusion of the Enzyme. The whole process takes about 4-5 hours to complete and Spencer now has a port-a-cath, which has made it much easier to start an IV.

We are now very used to the routine of ERT. I have many friends and relatives who pick up the girls from school each Tuesday while I stay with Spencer. Spencer has never once shown even a twinge of anxiety over receiving an IV treatment each week, he still skips all the way to the treatment room. This is partly because we use our time to watch movies, do crafts, and play Nintendo, and partly because we have made so many friends at the hospital who make each Tuesday something special. For those of you who are considering ERT when it becomes available for your child(I refuse to use the word "if")you can make this a positive experience for your family, not one to be feared and dreaded each week. There are several ways (Numby Stuff, EMLA creme, or cold spray) to help with the pain of the IV start and relieve emotional anxiety.

We have seen improvement in Spencer. This has been made evident by Spencer's participation on a basketball team. We can clearly see the changes in the stiffness of his joints when we watch him play. He would not have been able to play a year ago because of fatigue. He now keeps up with the other nine-year olds.

I know that there is concern over whether or not the Enzyme crosses the blood brain barrier or can stop nuerologic deterieration. I can not answer this question with scientific information. I can only tell you what I have seen in Spencer. A year ago, we were quite concerned about Spencer's IQ based on testing done at the University of Minnesota. Although Spencer is attending a private program for learning disabled children, he continues to function above his IQ and has made extraordinary gains in learning this year. We were concerned about his ability to learn new things, but we have recently stopped worrying about this. I am unsure whether or not this is an improvement because of the ERT, but we were told at the U of M to expect a downward trend in nuerologic function and that has not happened, in fact, just the opposite.

We continue to see changes in our sweet little girls that show us the ravages of MPS, but we have seen no further progression of the disease in Spencer. His appearance is subtley changing and he is showing less and less of the facial appearance of MPS. His headaches have stopped and he is healthy and strong. He feels that he is no different from any other kid and he is beginning to feel more like that to me, too.

We are in a very difficult situation while we wait on FDA approval. Our girls continue to decline while our little boy continues to improve. Because of the delays with approval and the changes we have seen in our seven year old, we too have been forced into making the decision to do a Bone Marrow transplant orwait for ERT to become available. Nothing about this is easy.

Please pray for quick FDA approval and availability of the Enzyme for each of the MPS disorders,

Amy Holland


Recent Filings: May 1999 (S-1 Filing)
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May 4, 1999

BIOMARIN PHARMACEUTICAL INC (BMRN)
S-1 Filing (SEC form S1)

BioMarin Pharmaceutical Inc. is a leading developer of carbohydrate enzyme therapies for debilitating, life-threatening, chronic genetic disorders and other diseases and conditions. In October 1998, we completed the primary evaluation for the pivotal clinical trial of our lead enzyme replacement product candidate, BM101, for the treatment of mucopolysaccharidosis-I or MPS- I. Based on the data from that trial, we intend to complete the filing of a BLA with the FDA in the second half of 1999. We have a joint venture with Genzyme Corporation for the worldwide development and commercialization of BM101.

MPS-I is a life-threatening genetic disorder caused by the lack of a sufficient quantity of the enzyme (alpha)-L-iduronidase, which affects about 3,400 patients in developed countries, including approximately 1,000 in the United States and Canada. Patients with MPS-I have multiple debilitating symptoms resulting from the buildup of carbohydrates in all tissues in the body. These symptoms include delayed physical and mental growth, enlarged livers and spleens, skeletal and joint deformities, airway obstruction, heart disease and impaired hearing and vision. If untreated, most children diagnosed with MPS-I will die from complications associated with the disease before adulthood.

BM101 is a specific form of (alpha)-L-iduronidase that is intended to replace a deficiency of (alpha)-L-iduronidase in MPS-I patients. In October 1998, we completed the primary evaluation period for our pivotal clinical trial for BM101. This clinical trial treated ten patients with MPS-I for a period of six months at five medical centers in the United States. BM101 met the primary endpoints in its pivotal trial, reducing liver or spleen sizes in eight of ten patients and lowering urinary carbohydrate levels in all ten patients. In addition, various secondary endpoints were reached in each of the patients. We received notice from the FDA that our BLA will receive fast track designation for the treatment of the more severe forms of MPS-I, which account for approximately 60% of all cases. The FDA has granted BM101 an orphan drug designation giving us exclusive rights to market BM101 to treat MPS-I for seven years from the date of FDA approval if BM101 is the first (alpha)-L-iduronidase drug to be approved by the FDA for the treatment of MPS-I.

In September 1998, we established a joint venture with Genzyme for the worldwide development and commercialization of BM101 for the treatment of MPS- I. Our responsibilities within the joint venture include obtaining U.S. regulatory approvals as well as manufacturing and process development. Genzyme is responsible for obtaining international regulatory approvals, worldwide sales and marketing as well as pricing and reimbursement. We will share expenses and profits from the joint venture equally with Genzyme. Genzyme invested $8.0 million upon signing the agreement and has agreed to purchase $10.0 million of common stock at the initial public offering price in a private placement concurrent with this offering. Genzyme has committed to pay us an additional $12.1 million upon approval of the BLA for BM101.

We are also developing enzyme replacement therapies for other life-threatening genetic diseases. There are nine additional MPS disorders caused by single enzyme deficiencies. We are developing BM102 for the treatment of MPS-VI. We received an orphan drug designation for BM102 to treat MPS-VI and intend to file an IND for the use of BM102 to treat MPS-VI in the fourth quarter of 1999. We are also developing carbohydrate enzymes intended to improve burn debridement and act as anti-fungals. Through a wholly-owned subsidiary, we provide carbohydrate analysis to research institutions and commercial laboratories.

Our strategy is to: (1) focus on drug candidates with known biology and low technical risk, (2) target products that address life-threatening conditions that may be developed and approved quickly, (3) pursue well-defined, niche markets, (4) develop a direct sales and marketing organization for select markets and (5) enhance enzymatic expertise through our wholly-owned subsidiary, Glyko, Inc.

Recent Filings: May 1999 (S-1 Filing)
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Editor's Note: The following is an excerpt from a recent Genzyme Press Release.

Genzyme General Posts Second-Quarter EPS of $.46

Date: July 22, 1999

Therapeutics Clinical Development Programs

Genzyme and BioMarin Pharmaceutical Inc. are jointly preparing a biologics license application (BLA) for alpha-L-iduronidase, which is being developed as a treatment for patients with MPS I. The companies are developing a protocol for a post-approval clinical study, which has been requested by the Food and Drug Administration. Post-approval—or phase IV—studies are often required for products that are granted accelerated review. As a result, the rolling filing of the BLA is now expected to begin late in the third quarter, with product launch expected mid-year 2000.


Editor's Note: The following is from a recent Genzyme Press Release.

Genzyme and Biomarin Announce Phase 3 Trial of Aldurazyme™ for MPS-I

November 22, 2000

Genzyme General (Nasdaq: GENZ) and BioMarin Pharmaceutical Inc. (Nasdaq and Swiss SWX New Market: BMRN) announced on November 22 that they are initiating a pivotal Phase 3 trial of Aldurazyme™ (laronidase), and expect to treat the first patient in the trial by early December. The product, recombinant alpha-L-iduronidase, is an enzyme replacement therapy for patients with MPS-I, also known as Hurler, Hurler-Scheie and Scheie diseases. Genzyme and BioMarin have received Orphan Drug designation and Fast-Track status for Aldurazyme from the U.S. Food and Drug Administration.

In an initial clinical trial, Aldurazyme has shown safety and promising clinical results. If the Phase 3 trial confirms the initial safety and efficacy profile of the drug, the companies will submit for marketing approval in the U.S., Europe, Canada and other countries in order to provide Aldurazyme therapy to the thousands of patients who currently suffer from this life-threatening disease.

In 1998, Genzyme and BioMarin formed BioMarin/Genzyme LLC to develop and commercialize Aldurazyme throughout the world.

BioMarin specializes in the development and commercialization of therapeutic enzyme products. Since inception in 1997, BioMarin has applied its proprietary enzyme technology to develop products for lysosomal storage diseases and for the treatment of serious burns. Glyko, Inc., a BioMarin subsidiary, provides analytical and diagnostic products and services in the area of carbohydrate biology.

Genzyme General develops and markets therapeutic products and diagnostic products and services. Genzyme General has three therapeutic products on the market and a strong pipeline of products in development focused on the treatment of genetic disorders. Genzyme General is a division of the biotechnology company Genzyme Corporation.

This press release contains forward-looking statements, including statements regarding: the expected timing of dosing patients in a Phase 3 trial; the clinical potential of Aldurazyme; anticipated submissions for regulatory approvals of Aldurazyme™ in the U.S. and Europe; and the potential market introduction of Aldurazyme. Actual results may differ materially from those contained in these forward-looking statements as a result of a number of factors, including: the actual safety and efficacy of Aldurazyme; the enrollment rates for the Phase 3 clinical trial; the results of clinical trials; the ability to manufacture sufficient amounts of Aldurazyme for development and commercialization activities; the timing and content of submissions to and decisions made by the FDA, the European Agency for the Evaluation of Medicine Products and other regulatory authorities; the continued funding of the joint venture; decisions made by physicians and third-party payers regarding the use of! , and reimbursement for, Aldurazyme; our ability to obtain and maintain adequate patent and other proprietary rights protection for Aldurazyme; the scope, validity and enforceability of patents and other proprietary rights held by third parties related to therapies for MPS-1 and the actual impact of such patents and other rights on our ability to commercialize Aldurazyme; the competitive environment for therapies for MPS-1; and the risks and uncertainties described in Genzyme’s and BioMarin’s reports filed with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including Exhibit 99.2 to Genzyme’s Annual Report on Form 10-K for the year ended December 31, 1999, as amended. GENZ stock is a series of common stock of Genzyme Corporation. Therefore, holders of GENZ stock are subject to all of the risks and uncertainties described in the aforementioned reports filed by Genzyme Corporation.

Aldurazyme™ is a trademark of BioMarin/Genzyme LLC. All rights reserved.



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