Press Releases from Pharmaceutical Companies

Shire presents positive results of Hunter syndrome pivotal clinical trial at the American Society of Human Genetics Annual Meeting

Shire Pharmaceuticals Group announced 28 October at the Annual Meeting of The American Society of Human Genetics, further results of its pivotal clinical trial evaluating its investigational human enzyme replacement therapy, idursulfase, for the treatment of Hunter Syndrome.

Breath stir the fit bottom or begins the lively Focus on writing paragraphs and essays 2nd edition pdf, Purpose of literature review in dissertation, Thesis topics in logistics and supply chain management elapse. Liquor drown the raw blow. Anchor ticked a last wreck, and owning the tiny plead. Bottle knew an all barge or avoids a mere island, in sum, bell corded the ill thing, and sells a sweet bet. Run erects the pale chest. Boat dating the cold search. Arc soled an idle spade.

The primary efficacy endpoint of the trial was a composite of two clinical measures – forced vital capacity (FVC) and 6-minute walk test (6MWT). As previously reported, patients receiving the weekly dosing regimen of 0.5 mg/kg of idursulfase showed a statistically significant difference (p=0.0049) compared to placebo. Results presented by Joseph Muenzer, M.D., Ph.D., of the University of North Carolina at Chapel Hill, indicated that patients receiving the every other week dosing regimen of idursulfase also showed a statistically significant difference (p=0.0416) compared to placebo when measuring the composite. Treatment with idursulfase was generally well-tolerated by patients in the trial.

Other results presented included urine GAG levels, liver and spleen volume, cardiac left ventricular volume, and joint range of motion.

Commenting on the trial results, Dr. Muenzer said “Data from this study are very

encouraging for patients and families living with Hunter syndrome. I am excited about the potential of idursulfase as the first treatment option for patients, once approved.”

As previously announced, Shire expects to file for regulatory approval of idursulfase in both the United States and Europe in the fourth quarter of 2005.

Trial Design

The AIM study (“Assessment of I2S in MPS II”) was a Phase II/III double-blind, placebo- controlled clinical trial conducted at nine sites around the world, including the United States, the United Kingdom, Germany and Brazil. The primary goal of the study was to evaluate the safety and efficacy of 0.5 mg/kg of idursulfase administered weekly compared to placebo. Additionally, the trial evaluated 0.5 mg/kg of idursulfase every other week compared to placebo. Ninety-six patients with Hunter syndrome were randomized to one of three groups with each patient receiving a total of 52 infusions of either idursulfase, idursulfase alternating weekly with placebo, or placebo. Of the 96 who enrolled, 94 completed the 52 week study and they all elected to participate in the open-label extension study of idursulfase at a dose of 0.5 mg/kg weekly.

Trial Results

Six minute walk test (6MWT)

In the weekly dosing regimen, the difference in meters walked was 35 meters compared to placebo (p=0.0131) and in the every other week idursulfase group, the difference in meters walked was 24 meters, compared to placebo (p=0.0732).

Forced Vital Capacity (FVC)

Model adjusted percent predicted FVC in the weekly group was 4.3% greater compared to placebo (p=0.0650); the every other week group showed no treatment difference in percent predicted FVC over placebo (p=0.9531).

Urinary GAG Levels

Urinary GAG levels were significantly lower in patients being treated with idursulfase in both the weekly or every other week dosing regimen compared to patients receiving placebo (p<0.0001). Among all 64 idursulfase treated patients, 26 patients had normalized urine GAG levels at week 53. None of the placebo patients had normalized urine GAG levels by week 53.

Liver and Spleen Size

Combined liver and spleen volume, as determined by MRI, decreased significantly from baseline to week 53 for patients receiving idursulfase weekly (-25.8%) or every other week (-23.7%), (p<0.0001 for both). Patients receiving placebo showed a volume increase of 0.3% in these organs over the same time period.

Left Ventricular Mass (LVM)

Of the 96 enrolled patients, 33 had an enlarged left ventricle at the initiation of the clinical trial (15 in the weekly group, and 9 each in the every other week and placebo groups). Patients in the idursulfase weekly group who had an enlarged left ventricle at the initiation of the clinical trial showed a mean reduction in LVM index of 14.1% following 52 weeks of treatment, compared with patients receiving placebo who exhibited a mean increase of 4.3% (p=0.1524). For patients treated every other week, there was a mean decrease in LVM index of 9.6% as compared to the 4.3% increase in the placebo group (p=0.2893).

Joint Range of Motion

There were no statistically significant differences between treatment groups for Global Joint Range of Motion Score, however there were improvements in elbow (p=0.0476) and shoulder joint mobility (p=0.0797) with weekly idursulfase compared to placebo.

Safety

Treatment with idursulfase was generally well-tolerated by patients in the trial. The most common adverse events observed were associated with the clinical manifestations of Hunter syndrome. Of the adverse events considered possibly related to idursulfase, infusion related reactions were the most common and were generally mild. There were two patient deaths during the study, both of which were considered unrelated to treatment with idursulfase. Of the 64 idursulfase-treated patients, 6 patients tested positive for IgG antibodies, and 2 patients tested positive for IgM antibodies at some time during the course of the study. No IgE antibodies were observed. No patient withdrew from the trial due to an adverse event considered related to idursulfase.

Proposed acquisition of Transkaryotic Therapies Inc.

Shire Pharmaceuticals Group plc announced July 27,2005, that the proposed acquisition of Transkaryotic Therapies, Inc. (“TKT”) was approved by Shire’s shareholders on July 27, 2005. The acquisition is now expected to complete on July 28, 2005.

Shire expects to pay approximately $1.6bn or $37 per common share in cash as consideration for the TKT shares in accordance with the terms of the acquisition.

Shire Chief Executive, Matthew Emmens, commented: “This is great news for Shire and TKT. This acquisition delivers on our strategy and brings a new drug development platform and expertise within a specialty area as well as further expansion into the European markets. We expect that this move will broaden our revenue base while continuing to grow our profits and further build our pipeline in a relatively low risk area of Enzyme Replacement Therapy.

“TKT transition will start immediately and David Pendergast will join our senior management team. We look forward to working with our new colleagues on the development and commercialization of their existing pipeline. The next important milestones this year are; the filing of I2S with the US Food and Drug Administration expected before the end of this year, as well as the publication of phase 1 clinical data for GA-GCB, a treatment for Gaucher’s disease.

“As previously stated, this acquisition is expected to significantly enhance Shire’s sales and EPS growth beyond 2007 and sustain Shire’s consistent operating margin performance.”

Chief Executive Officer of TKT, David Pendergast, Ph.D., said: “This is a tremendous opportunity for our business and our employees. We look forward to advancing our pipeline with the added expertise and resources that Shire brings to us. It is also great news for patients suffering from rare genetic disorders as it will enable us to introduce effective, life saving treatments that can make such a difference to their lives.”

TKT Reports Positive Top-Line Results of Hunter Syndrome Pivotal Trial

Primary Endpoint Achieves Statistical Significance

Transkaryotic Therapies, Inc. announced June 20, 2005 positive top-line results from the company's pivotal Phase III clinical trial evaluating its investigational human enzyme replacement therapy, iduronate-2-sulfatase (I2S), for the treatment of patients with Hunter syndrome. Hunter syndrome, also known as MPS II, is a rare, life-threatening genetic disorder with no available treatment. In the trial, patients who received 0.5 mg/kg of I2S on a weekly basis showed a statistically significant improvement in the primary efficacy endpoint (p=0.0049) compared to patients receiving placebo. Based on these results, TKT expects to file for regulatory approval of I2S in both the United States and Europe in the fourth quarter of 2005.

The primary efficacy endpoint of the trial, also referred to as the AIM study ("Assessment of I2S in MPS II") was a composite endpoint of two clinical measures previously used to assess clinical benefit in MPS disorders - forced vital capacity and six-minute walk test. The mean improvement from baseline to week 53 in percent predicted forced vital capacity was 3.4% in patients receiving I2S compared to 0.8% in patients receiving placebo. The mean increase from baseline to week 53 in the distance walked by patients receiving I2S was 44 meters as compared to 7 meters in the placebo group.

Joseph Muenzer, M.D., Ph.D., of the University of North Carolina at Chapel Hill, an internationally recognized leader in the diagnosis and treatment of MPS disorders and the lead investigator of the AIM study said, "These findings are very encouraging for the medical and patient communities as we believe enzyme replacement therapy can bring new hope for patients and families addressing many of the symptoms associated with Hunter syndrome."

Treatment with I2S was generally well-tolerated by patients in the trial. The most common adverse events observed were associated with the clinical manifestations of Hunter syndrome. Of the adverse events considered possibly related to I2S, infusion related reactions were the most common and were generally mild. No patient withdrew from the trial due to an adverse event considered related to I2S.

"We are extremely excited about the outcome of the study. In addition, we are very thankful to all the patients and their families who participated in this one year trial. Their commitment to this program was instrumental in generating the data which we believe will support regulatory approval of I2S," said Kip Martha, M.D., Senior Vice President and Chief Medical Officer of TKT.

TKT expects full data will be presented at a medical meeting in the autumn of 2005.

Trial Design

The AIM study was a Phase III double-blind, placebo-controlled clinical trial conducted at nine sites around the world, including the United States, the United Kingdom, Germany and Brazil. The primary goal of the study was to evaluate the safety and efficacy of 0.5 mg/kg of I2S administered weekly compared to placebo. Additionally, the trial evaluated 0.5 mg/kg of I2S every other week compared to placebo. Ninety-six patients with Hunter syndrome were randomized to one of three groups with each patient receiving a total of 52 infusions of either I2S, I2S alternating weekly with placebo, or placebo. Of the 96 who enrolled, 94 completed the study and they all elected to participate in the open-label extension study of I2S at a dose of 0.5 mg/kg weekly.

New Website Offers Comprehensive Information on Hunter Syndrome

Transkaryotic Therapies, Inc announced March 28, 2005 the launch of a new educational website focused on Hunter syndrome. Hunter syndrome, also referred to as MPS II, is a rare disorder in a class referred to as mucopolysaccharidoses or MPS. The site, http://www.hunterpatients.com, is a resource center for the Hunter community to access information about the genetics, diagnosis and management of Hunter syndrome as well as information about the drug development process.

TKT recently completed a multinational Phase III clinical trial evaluating an investigational enzyme replacement therapy for the treatment of Hunter syndrome. Results of the study are expected to be announced in June 2005 and, if positive, the company will file for regulatory approval in the U.S. and Europe in the second half of 2005.

"As we continue to learn more about MPS disorders and as new treatments are being developed, we hope to improve awareness of these rare and often life-threatening disorders. Easy access to information is the best way for families and practitioners to stay informed about new developments in the area," said Joseph Muenzer, M.D., Ph.D., of the University of North Carolina at Chapel Hill, an internationally recognized leader in the diagnosis and treatment of MPS disorders and the lead investigator of TKT's Phase III trial. "The launch of this site marks an important step toward offering patients, families and healthcare providers access to important medical and educational information relating to Hunter syndrome."

The website provides a comprehensive overview of Hunter syndrome, including resources for patients and healthcare professionals, information on clinical trials and a patient outcomes survey, as well as the ability to stay informed as new information about Hunter syndrome becomes available on the site. In addition, TKT expects to update and expand the site on a regular basis.

BioMarin Announces U.S. Launch of Naglazyme for MPS VI

BioMarin Pharmaceutical Inc. announced June 21, 2005 that Naglazyme(TM) (galsulfase) is now available in the United States as the first specific therapy approved for the treatment of individuals with mucopolysaccharidosis VI (MPS VI). Naglazyme was approved on May 31, 2005 by the U.S. Food and Drug Administration (FDA) and was shipped to distributors on Monday, June 20. The drug is being shipped to physicians this week. Naglazyme was developed by BioMarin and will be commercialized by the company's U.S.-based sales force. Naglazyme is indicated for patients with MPS VI. Naglazyme has been shown to improve walking and stair-climbing capacity.

"With the commercial launch of Naglazyme, individuals with MPS VI now have an approved treatment option that specifically addresses the underlying cause of this progressive and debilitating disease," stated Jean-Jacques Bienaime, Chief Executive Officer and Director of BioMarin. "Naglazyme is the second product developed by BioMarin to receive FDA approval and the first such product that we are commercializing on our own. We have prepared extensively for this moment and are optimistic that our preparation will result in a robust product launch."

In a separate release, BioMarin announced the appointment of Stephen Aselage to the position of Senior Vice President, Global Commercial Operations, effective July 1, 2005. BioMarin's commercial team includes four medical science liaisons who will be responsible for providing support to infusion centers and physicians who administer Naglazyme. The BioMarin sales force has mounted a disease awareness campaign targeted toward pediatricians and sub-specialists who are involved in the multi-disciplinary care of patients with MPS disorders to help drive new patient identification. Additionally, BioMarin has launched BioMarin Physician and Patient Support (BPPS), a free and confidential service established to assist patients and caregivers in their effort to receive insurance reimbursement for treatment with Naglazyme.

Naglazyme is administered once weekly via intravenous infusion and is dosed at 1 milligram of drug per kilogram of body weight. The annual cost of treatment will vary considerably according to each patient's weight.

ATU Program Under Way in France

In advance of product approval, BioMarin has received temporary use authorization (ATU) from regulatory authorities in France for named patient basis sales. Three patients who met certain selection criteria have begun to receive Naglazyme treatment. BioMarin expects to book revenue from these named patient basis sales and will continue to assist patients in Europe wherever possible prior to product approval in the European Union.

BioMarin Announces FDA Approval for Naglazyme

First Specific Therapy Approved for the Treatment of MPS VI

BioMarin Pharmaceutical Inc. announced June 1, 2005 that the U.S. Food and Drug Administration (FDA) has granted marketing approval for Naglazyme(TM) (galsulfase), the first specific therapy approved for the treatment of mucopolysaccharidosis VI (MPS VI). As the first drug ever approved for MPS VI, Naglazyme has been granted orphan drug status in the United States, which confers seven years of market exclusivity. BioMarin plans to launch Naglazyme in the United States in approximately 30 days. As post-marketing clinical commitments, BioMarin has agreed with the FDA to evaluate the effect of Naglazyme treatment on skeletal dysplasia in patients under the age of 1 and to maintain a clinical surveillance program to monitor patients on commercial therapy; no extension study of Phase 3 patients was required.

Clinical trials have demonstrated that Naglazyme provides clinically important benefits for MPS VI patients, specifically, improved endurance as demonstrated by the 12-minute walk test and 3-minute stair climb. Naglazyme reduced the excess carbohydrates (glycosaminoglycans, or 'GAGs') that are excreted in the urine of patients with MPS VI, an indication of enzymatic bioactivity.

"I have observed the positive effect that enzyme replacement therapy with Naglazyme can have on MPS VI patients, and I am very pleased that it will soon be made commercially available to those who need it," stated Paul Harmatz, M.D., Associate Director of the Pediatric Clinical Research Center at Children's Hospital & Research Center at Oakland, California, and Principal Investigator of the Phase 3 clinical trial of Naglazyme. "With Naglazyme now approved, physicians, for the first time, have a therapeutic to treat the underlying cause of MPS VI, increasing their ability to provide better care for MPS VI patients with this life-threatening disease."

"The approval of Naglazyme is a significant milestone for those whose life has been affected by MPS VI and for BioMarin," stated Jean-Jacques Bienaime, Chief Executive Officer of BioMarin. "The disease burden of MPS VI is enormous for patients, families and physicians. Naglazyme holds a very real possibility for making MPS VI a more manageable disease." Mr. Bienaime continued, "BioMarin developed Naglazyme on its own and now, with our U.S.- based sales force in place, we are ready to bring it to market. Our efforts to identify individuals with MPS VI in the years leading up to this day have positioned us to rapidly get patients on therapy come product launch. I would like to thank the individuals with MPS VI and their families and physicians as well as BioMarin employees for their years of hard work and dedication toward making Naglazyme for MPS VI a reality."

An application to market Naglazyme is currently pending in the European Union. BioMarin expects to receive an opinion from the European Commission in the fourth quarter of 2005, and if positive, final approval in early 2006.

Phase 3 Clinical Trial and Extension Study Results

BioMarin completed a 24-week, Phase 3, multi-center, double-blind, placebo-controlled trial involving 39 patients. Patients were randomized on a one-to-one basis into a Naglazyme treatment group or a placebo control group and received a weekly intravenous infusion of either 1.0 mg/kg of Naglazyme or placebo solution. During the 24-week period, 19 patients received weekly intravenous infusions of Naglazyme and 20 patients received weekly placebo infusions. One patient in the placebo group dropped out of the trial for reasons unrelated to treatment. All 38 patients who completed the trial elected to receive Naglazyme in an ongoing open-label extension study.

Efficacy Data

After 24 weeks of treatment, patients receiving Naglazyme demonstrated a statistically significant improvement (p=0.025) in endurance compared to patients receiving placebo as measured by the change relative to baseline in the distance walked in 12 minutes. The Naglazyme-treated group showed greater mean increase in distance walked in 12 minutes compared to the placebo group. The model-derived mean difference measured as a change from baseline between patients receiving Naglazyme and patients receiving placebo after 24 weeks was 92 +/- 40 meters. Following an additional 24 weeks of treatment with Naglazyme in the extension study, for a total of 48 weeks, patients demonstrated further improvement in endurance as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, patients receiving Naglazyme since week one of the trial improved their mean walk distance an additional 36 +/- 97 meters.

After 24 weeks of treatment, patients receiving Naglazyme demonstrated an improvement (p=0.053) in stair-climbing ability compared to patients receiving placebo as measured by the change relative to baseline in the number of stairs climbed per minute. The Naglazyme-treated group showed greater mean increase in the rate of stairs climbed in three minutes compared to the placebo group. The model-derived mean difference measured as a change from baseline between patients receiving Naglazyme and patients receiving placebo after 24 weeks was 5.7 +/- 2.9 stairs per minute. Following an additional 24 weeks of treatment with Naglazyme in the extension study, from week 24 to week 48, patients receiving Naglazyme since week one of the trial improved their mean number of stairs climbed per minute by an additional 3 +/- 7 stairs.

After 24 weeks of treatment, patients receiving Naglazyme experienced a statistically significant reduction (p<0.001) of GAGs excreted in the urine, compared to patients receiving placebo. The average urinary GAG reduction in patients receiving Naglazyme after 24 weeks was 75.5 percent. This initial reduction in urinary GAG levels was maintained following an additional 24 weeks of treatment in the extension study.

While in the extension study, patients who receive placebo solution during the initial 24-week trial demonstrated an improvement in endurance following 24 weeks of treatment with Naglazyme as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, the original placebo group demonstrated a mean increase of 65 meters relative to week 24 values. These patients also demonstrated an average improvement in stair-climbing ability as measured by stairs climbed in three minutes, relative to baseline, of 5.7 stairs per minute following 24 weeks of treatment with Naglazyme. Additionally, patients initially receiving placebo demonstrated a reduction in urinary GAG levels following 24 weeks of treatment with Naglazyme comparable to that observed for those treated in the initial 24-week, double-blind portion of the trial.

Safety Data

Data from the Phase 3 clinical trial and extension study indicate that Naglazyme was generally safe. The most common adverse events observed in clinical trials in Naglazyme-treated patients were headache, fever, arthralgia, vomiting, upper respiratory infections, abdominal pain, diarrhea, ear pain, cough, and otitis media. Over 95 percent of the infusion-related adverse events were considered mild or moderate and were easily managed. Infusion-related adverse events commonly included fever, chills/rigors, headache, rash, and mild to moderate urticaria. Severe reactions included angioneurotic edema, hypotension, dyspnea, bronchospasm, respiratory distress, apnea, and urticaria. No patients discontinued Naglazyme infusions for adverse events and all patients that completed the double-blind portion of the trial continue to receive weekly infusions of Naglazyme. Nearly all patients developed antibodies as a result of treatment, but the level of the immune response did not correlate with adverse events or impact the improvements experienced in endurance. Evaluation of airway patency should be considered prior to the initiation of treatment. Consideration to delay Naglazyme infusion should be given when treating patients who present with an acute febrile or respiratory illness.

BioMarin's Phase 3 Extension Study of rhASB in MPS VI Demonstrates Additional Improvements in Endurance

Further Improvements in Patients Receiving rhASB and Significant Improvements in Patients Previously Receiving Placebo

BioMarin Pharmaceutical Inc. March 9 2005 announced positive results from the Phase 3 extension study of rhASB (galsulfase), the company's investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). Data from the study demonstrate that patients who received rhASB for an additional 24 weeks, for a total of 48 weeks, continued to experience improved endurance. Patients who initially received placebo and then received rhASB for 24 weeks also experienced improved endurance. The data were presented by Stuart Swiedler, M.D., Ph.D., Senior Vice President of Clinical Affairs at BioMarin, at the annual meeting of the Society for Inherited Metabolic Diseases held in Pacific Grove, California.

Dr. Swiedler stated, "We are pleased to see continued benefit experienced by MPS VI patients receiving extended treatment with rhASB for MPS VI. The Phase 3 extension data further confirm the positive safety and efficacy profile of rhASB we have observed since the initiation of the clinical program, and we are working to make this therapy commercially available to individuals with MPS VI in the United States in the second half of the year."

Phase 3 Extension Study Design

All 38 patients who completed the initial 24-week, Phase 3, multi-center, double-blind, placebo-controlled trial were enrolled in the open-label extension study to further evaluate the safety and efficacy of rhASB. Patients who received rhASB during the initial 24-week, placebo-controlled portion of the trial continued to receive weekly 1.0 mg/kg infusions of rhASB in the extension study. Patients who initially received placebo during the placebo-controlled portion of the trial received 1.0 mg/kg of rhASB via weekly infusion during the extension study. Patients were evaluated at pre-defined, six-week intervals to assess changes in primary and secondary efficacy endpoints and the safety and tolerability of weekly rhASB infusions. Results of the study for the groups are summarized below:

Results from Patients Receiving 48 Weeks of rhASB

  • Patients demonstrated further improvement in endurance following an additional 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean walk distance an additional 36 meters for a total of 145 meters for the 48-week period.
  • Patients demonstrated a further improvement in endurance following 48 weeks of treatment with rhASB as measured by the number of stairs climbed in three minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean number of stairs climbed per minute by an additional 2.9 stairs for a total of a 10.4 stairs-per-minute improvement for the 48-week period.
  • The initial reduction in urinary glycosaminoglycan (GAG) levels, an in vivo measure of enzyme activity, was maintained from week 24 to week 48. Urinary GAG levels were reduced by 75.5 percent during the initial 24-week period.

Results from Patients Receiving 24 Weeks of rhASB

  • Patients initially receiving placebo demonstrated improvements in endurance following 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, the original placebo group demonstrated a mean increase of 65 meters relative to week 24 values.
  • Patients initially receiving placebo solution demonstrated an average improvement in endurance as measured by stairs climbed in three minutes, relative to baseline, of 5.7 stairs per minute following 24 weeks of treatment with rhASB.
  • Patients initially receiving placebo demonstrated a reduction in urinary GAG levels following 24 weeks of treatment with rhASB comparable to that observed for those treated in the initial 24-week, double-blind portion of the trial (p<0.001).

Data indicate that rhASB was generally safe and well-tolerated. The majority of adverse events reflected the underlying disease state or occurred during drug infusion. Over 95 percent of the infusion-related adverse events were considered mild or moderate and were easily managed. No patients discontinued rhASB infusions for adverse events and all patients that completed the double-blind portion of the trial continue to receive weekly infusions of rhASB. Nearly all patients developed antibodies as a result of treatment, but the level of the immune response did not correlate with adverse events or impact the improvements experienced in endurance.

FDA Accepts and Grants Six-Month Review for BioMarin's Marketing Application for rhASB for MPS VI PDUFA Date Set for May 31, 2005

BioMarin Pharmaceutical Inc. announced Feb. 1, 2005 that the U.S. Food and Drug Administration (FDA) has accepted for filing and assigned six-month review to the Biologics License Application (BLA) for rhASB (galsulfase), the company's investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). The FDA will take action on the application, under the Prescription Drug User Fee Act (PDUFA), by May 31, 2005. A six-month review is typically granted to drugs that, if approved, would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious or life-threatening disease. The FDA previously granted rhASB orphan drug designation, a designation conferred upon investigational products for diseases that affect fewer 200,000 patients in the United States. Products with orphan drug designation that are the first to be approved for a specific indication have seven years market exclusivity within the United States. About rhASB rhASB is an investigational enzyme replacement therapy designed to address the underlying enzyme deficiency associated with MPS VI. If approved, rhASB could become the first drug therapy for the treatment of MPS VI.

BioMarin's Phase 3 Extension Study of rhASB in MPS VI Demonstrates Additional Improvements in Endurance

Further Improvements in Patients Receiving rhASB and Significant Improvements in Patients Previously Receiving Placebo BioMarin Pharmaceutical Inc. announced March 9th positive results from the Phase 3 extension study of rhASB (galsulfase), the company's investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). Data from the study demonstrate that patients who received rhASB for an additional 24 weeks, for a total of 48 weeks, continued to experience improved endurance. Patients who initially received placebo and then received rhASB for 24 weeks also experienced improved endurance. The data were presented by Stuart Swiedler, M.D., Ph.D., Senior Vice President of Clinical Affairs at BioMarin, at the annual meeting of the Society for Inherited Metabolic Diseases held in Pacific Grove, California. Dr. Swiedler stated, "We are pleased to see continued benefit experienced by MPS VI patients receiving extended treatment with rhASB for MPS VI. The Phase 3 extension data further confirm the positive safety and efficacy profile of rhASB we have observed since the initiation of the clinical program, and we are working to make this therapy commercially available to individuals with MPS VI in the United States in the second half of the year." Phase 3 Extension Study Design All 38 patients who completed the initial 24-week, Phase 3, multi-center, double-blind, placebo-controlled trial were enrolled in the open-label extension study to further evaluate the safety and efficacy of rhASB. Patients who received rhASB during the initial 24-week, placebo-controlled portion of the trial continued to receive weekly 1.0 mg/kg infusions of rhASB in the extension study. Patients who initially received placebo during the placebo-controlled portion of the trial received 1.0 mg/kg of rhASB via weekly infusion during the extension study. Patients were evaluated at pre-defined, six-week intervals to assess changes in primary and secondary efficacy endpoints and the safety and tolerability of weekly rhASB infusions. Results of the study for the groups are summarized below: Results from Patients Receiving 48 Weeks of rhASB -- Patients demonstrated further improvement in endurance following an additional 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean walk distance an additional 36 meters for a total of 145 meters for the 48-week period. -- Patients demonstrated a further improvement in endurance following 48 weeks of treatment with rhASB as measured by the number of stairs climbed in three minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean number of stairs climbed per minute by an additional 2.9 stairs for a total of a 10.4 stairs-per-minute improvement for the 48-week period. -- The initial reduction in urinary glycosaminoglycan (GAG) levels, an in vivo measure of enzyme activity, was maintained from week 24 to week 48. Urinary GAG levels were reduced by 75.5 percent during the initial 24-week period. Results from Patients Receiving 24 Weeks of rhASB -- Patients initially receiving placebo demonstrated improvements in endurance following 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, the original placebo group demonstrated a mean increase of 65 meters relative to week 24 values. -- Patients initially receiving placebo solution demonstrated an average improvement in endurance as measured by stairs climbed in three minutes, relative to baseline, of 5.7 stairs per minute following 24 weeks of treatment with rhASB. -- Patients initially receiving placebo demonstrated a reduction in urinary GAG levels following 24 weeks of treatment with rhASB comparable to that observed for those treated in the initial 24-week, double-blind portion of the trial (p<0.001). Data indicate that rhASB was generally safe and well-tolerated. The majority of adverse events reflected the underlying disease state or occurred during drug infusion. Over 95 percent of the infusion-related adverse events were considered mild or moderate and were easily managed. No patients discontinued rhASB infusions for adverse events and all patients that completed the double- blind portion of the trial continue to receive weekly infusions of rhASB. Nearly all patients developed antibodies as a result of treatment, but the level of the immune response did not correlate with adverse events or impact the improvements experienced in endurance.

Genzyme Sues to Halt TKT Gaucher Trial TKT to Defend Patent Suit in Israel

Transkaryotic Therapies, Inc. (TKT) announced Jan. 24, 2005 that Genzyme Corporation has filed suit against TKT in the District Court of Tel-Aviv-Jaffa but not yet formerly served process on TKT. The suit claims that TKT's Phase I/II clinical trial evaluating its investigational Gene-Activated(R) glucocerebrosidase (GA-GCB) for the treatment of Gaucher disease infringes one or more claims of Israeli Patent No. 100,715. In addition, Genzyme filed a motion for preliminary injunction, including a request for an ex parte hearing and relief on the merits, to immediately seize and destroy all GA-GCB being used to treat patients in TKT's ongoing clinical trial and to prevent the company from submitting data generated from the clinical trial to regulatory agencies. The judge has already rejected Genzyme's request for ex parte relief. "We believe Genzyme's efforts to try and disrupt our ongoing clinical development of GA-GCB are an improper attempt to extend its monopoly in the area of Gaucher disease," said Kerry A. Flynn, Vice President of Intellectual Property and Licensing at TKT. "We do not believe we infringe any valid claim or that there is a reasonable likelihood that this unprecedented tactic will interrupt our clinical trial. We intend to honor our commitment to continue treating our Gaucher patients with GA-GCB." TKT is conducting an open-label Phase I/II study to evaluate the safety and clinical activity of GA-GCB. The study enrolled twelve patients with Type I Gaucher disease from several countries. TKT expects to report top-line data from this study in the second half of 2005. Gaucher disease is the most common of the inherited lysosomal storage diseases and is caused by a deficiency of the enzyme glucocerebrosidase. As a result of this deficiency, certain lipids accumulate in specific cells of the liver, spleen, and bone marrow causing significant clinical symptoms in the patient, including enlargement of the liver and spleen, hematologic abnormalities, and bone disease.

Genzyme Files for European Approval of Myozyme® For Treatment of Pompe Disease

Genzyme Corp. announced 20 December 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.

Genzyme, AGTC Announce Gene Therapy Collaboration

Genzyme Corporation and Applied Genetic Technologies (AGTC), a private development-stage biotechnology company, announced 6th December 2004 that they have entered into a research collaboration to jointly develop novel therapeutics involving gene therapy. Through the collaboration, Genzyme gains access to AGTC's extensive expertise using Adeno-Associated Virus (AAV) vectors to deliver genes to patients, including access to AGTC's novel high-yield manufacturing capabilities for AAV vectors. These vectors may have therapeutic advantages in several disease areas where Genzyme has active preclinical development programs, including lysosomal storage disorders, cardiovascular disease, central nervous system disorders, immune-mediated disorders, and others. Genzyme brings to the collaboration more than a decade of experience with gene therapy, involving multiple clinical trials in cardiovascular disease, oncology, and cystic fibrosis. Financial terms were not disclosed. "We are delighted to collaborate with an established biotechnology leader like Genzyme, which has contributed heavily to many advances in our understanding of gene therapy," said Sue Washer, CEO of AGTC. "This agreement is an important validation of AGTC's technology, and will position us to build on our early work in a number of therapeutic areas and enable us to bring products to market more efficiently." "Our work with AGTC will bring Genzyme an impressive technology platform, which includes a scalable, highly productive manufacturing capability with the potential to support future clinical trials and product development," said Sam Wadsworth, vice president, Translational Research at Genzyme. AGTC has licensed a significant portion of its intellectual property from the University of Florida where researchers originated this ground-breaking work in gene therapy. AGTC is developing novel therapeutics for patients with unmet medical needs utilizing the non-pathogenic adeno-associated virus. AGTC's first product candidate is a treatment for Alpha One Antitrypsin Deficiency, an inherited form of emphysema; Phase I trials are underway with a potential product launch in early 2009. AGTC's investors include Interwest Partners (Menlo Park, California), Intersouth Partners (Durham, North Carolina), MedImmune Ventures (Gaithersburg, Maryland) and Skyline Ventures (Palo Alto, California). The company is located in Gainesville, Florida in the University of Florida's business development park. 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. Genzyme's commitment to innovation continues today with research into novel approaches to cancer, heart disease, and other areas of unmet medical need. More than 7,000 Genzyme employees in offices around the globe serve patients in over 80 countries.

TKTs I2S for Hunter Syndrome Receives Office of Orphan Products Grant

CAMBRIDGE, Mass., Sept. 28 /PRNewswire-FirstCall/ -- Transkaryotic Therapies, Inc. (Nasdaq: TKTX) today announced that it has received a Development Grant from the FDA's Office of Orphan Products Development (OOPD) for iduronate-2-sulfatase (I2S), TKT's investigational enzyme replacement therapy for the treatment of Hunter syndrome, also known as MPS II, a rare, fatal disease. The $300,000 grant will pay for some costs of the company's ongoing pivotal trial. "We are grateful for this recognition of the importance of our efforts to develop I2S as a potential treatment for Hunter syndrome. We fully support the FDA's mission to encourage clinical development of products for rare diseases and to put agency resources behind these development efforts," said Michael J. Astrue, President and Chief Executive Officer of TKT. Since 1989, approximately 36 products supported by OOPD grants have received marketing approval by the U.S. Food and Drug Administration. Clinical studies conducted under an Investigational New Drug application for a rare disease qualify for consideration by the program. Grants of this size are typically awarded to drugs in Phase III clinical trials. The I2S pivotal trial, referred to as the AIM (Assessment of I2S in MPS II) study, is a fully enrolled trial designed to evaluate safety and efficacy of weekly and every-other week infusions of I2S administered at a dose of 0.5 mg/kg. Patients will receive a total of fifty-two infusions of either I2S (patients randomized to the weekly dosing regimen), I2S alternating with placebo (patients randomized to the every other week regimen), or placebo. The AIM study is a twelve-month, randomized, double-blind, placebo-controlled trial being conducted at nine sites around the world. The primary efficacy endpoint in the trial is a single composite variable which combines two clinical measurements: forced vital capacity as a measure of respiratory function and the six-minute walk test as a measure of functional capacity. Additional efficacy endpoints include measurements of joint range of motion and combined liver/spleen size. TKT expects top-line results from the AIM study in the second quarter of 2005 and, if positive, the company expects to submit applications for marketing approval in both the United States and Europe in the second half of 2005.

TKT Receives Fast Track Designation For Iduronate-2-Sulfatase for Hunter Syndrome.

CAMBRIDGE, Mass., July 15 /PRNewswire-FirstCall/ -- Transkaryotic Therapies, Inc. (Nasdaq: TKTX) today announced that it has received fast track designation from the U.S. Food and Drug Administration (FDA) for iduronate-2- sulfatase (I2S) to treat Hunter syndrome (MPS II). TKT commenced a pivotal study with I2S in September 2003. The study, referred to as AIM (Assessment of Iduronate-2-sulfatase in MPS II) is a twelve-month, randomized, double-blind, placebo-controlled trial evaluating I2S in 96 patients. TKT expects top-line results from the AIM study in the second quarter of 2005 and, if positive, the company expects to submit applications for marketing approval in both the United States and Europe in the second half of 2005. "We are pleased that the FDA has given I2S this important designation," said Michael J. Astrue, President and Chief Executive Officer of TKT. "We are committed to bringing this treatment to patients as quickly as possible."

About Fast Track Designation

Under the FDA Modernization Act of 1997, fast track regulations are designed to facilitate the development of products to treat serious or life- threatening diseases where an unmet medical need exists. Fast track regulations are also designed to expedite the review process for designated products, including the potential for companies to submit marketing applications on a rolling basis.

TKT to Present Research on Intrathecal Delivery of I2S for Hunter Syndrome at ASHG New Data on Lysosomal Storage Disease Programs to be Presented

CAMBRIDGE, Mass., Sept. 20/PRNewswire-FirstCall/ -- Transkaryotic Therapies, Inc. (Nasdaq: TKTX) today announced that its research findings evaluating intrathecal delivery of iduronate-2-sulfatase (I2S) in an animal model will be presented at the American Society of Human Genetics 54th Annual Meeting in Toronto. I2S is TKT’s investigational enzyme replacement therapy being developed for the treatment of Hunter syndrome, also referred to as MPS II, a rare and often fatal disease. These research findings will be presented by Dr. Justin Lamsa of TKT at a poster session from 5:00 – 7:00 p.m. on Thursday, October 28, 2004. Recently, TKT made the decision to advance a program evaluating delivery of I2S directly into the central nervous system into preclinical development. The company expects to file an Investigational New Drug Application to commence human clinical trials of its I2S CNS program in the first half of 2006. “As part of our ongoing efforts to broadly serve patients suffering from rare diseases, we are committed to understanding how best to administer treatments targeting the central nervous system. Our hope is that intrathecal injection or other delivery methods may be feasible in treating patients affected with Hunter syndrome who develop central nervous system complications,” said Michael Heartlein, Ph.D., Vice President, Research at TKT.

Shire presents positive results of Hunter syndrome pivotal clinical trial at the American Society of Human Genetics Annual Meeting

Shire Pharmaceuticals Group announced 28 October at the Annual Meeting of The American Society of Human Genetics, further results of its pivotal clinical trial evaluating its investigational human enzyme replacement therapy, idursulfase, for the treatment of Hunter Syndrome.


The primary efficacy endpoint of the trial was a composite of two clinical measures – forced vital capacity (FVC) and 6-minute walk test (6MWT). As previously reported, patients receiving the weekly dosing regimen of 0.5 mg/kg of idursulfase showed a statistically significant difference (p=0.0049) compared to placebo. Results presented by Joseph Muenzer, M.D., Ph.D., of the University of North Carolina at Chapel Hill, indicated that patients receiving the every other week dosing regimen of idursulfase also showed a statistically significant difference (p=0.0416) compared to placebo when measuring the composite. Treatment with idursulfase was generally well-tolerated by patients in the trial.

Other results presented included urine GAG levels, liver and spleen volume, cardiac left ventricular volume, and joint range of motion.

Commenting on the trial results, Dr. Muenzer said “Data from this study are very

encouraging for patients and families living with Hunter syndrome. I am excited about the potential of idursulfase as the first treatment option for patients, once approved.”


As previously announced, Shire expects to file for regulatory approval of idursulfase in both the United States and Europe in the fourth quarter of 2005.


Trial Design

The AIM study (“Assessment of I2S in MPS II”) was a Phase II/III double-blind, placebo- controlled clinical trial conducted at nine sites around the world, including the United States, the United Kingdom, Germany and Brazil. The primary goal of the study was to evaluate the safety and efficacy of 0.5 mg/kg of idursulfase administered weekly compared to placebo. Additionally, the trial evaluated 0.5 mg/kg of idursulfase every other week compared to placebo. Ninety-six patients with Hunter syndrome were randomized to one of three groups with each patient receiving a total of 52 infusions of either idursulfase, idursulfase alternating weekly with placebo, or placebo. Of the 96 who enrolled, 94 completed the 52 week study and they all elected to participate in the open-label extension study of idursulfase at a dose of 0.5 mg/kg weekly.


Trial Results


Six minute walk test (6MWT)

In the weekly dosing regimen, the difference in meters walked was 35 meters compared to placebo (p=0.0131) and in the every other week idursulfase group, the difference in meters walked was 24 meters, compared to placebo (p=0.0732).


Forced Vital Capacity (FVC)

Model adjusted percent predicted FVC in the weekly group was 4.3% greater compared to placebo (p=0.0650); the every other week group showed no treatment difference in percent predicted FVC over placebo (p=0.9531).


Urinary GAG Levels

Urinary GAG levels were significantly lower in patients being treated with idursulfase in both the weekly or every other week dosing regimen compared to patients receiving placebo (p<0.0001). Among all 64 idursulfase treated patients, 26 patients had normalized urine GAG levels at week 53. None of the placebo patients had normalized urine GAG levels by week 53.


Liver and Spleen Size

Combined liver and spleen volume, as determined by MRI, decreased significantly from baseline to week 53 for patients receiving idursulfase weekly (-25.8%) or every other week (-23.7%), (p<0.0001 for both). Patients receiving placebo showed a volume increase of 0.3% in these organs over the same time period.


Left Ventricular Mass (LVM)

Of the 96 enrolled patients, 33 had an enlarged left ventricle at the initiation of the clinical trial (15 in the weekly group, and 9 each in the every other week and placebo groups). Patients in the idursulfase weekly group who had an enlarged left ventricle at the initiation of the clinical trial showed a mean reduction in LVM index of 14.1% following 52 weeks of treatment, compared with patients receiving placebo who exhibited a mean increase of 4.3% (p=0.1524). For patients treated every other week, there was a mean decrease in LVM index of 9.6% as compared to the 4.3% increase in the placebo group (p=0.2893).


Joint Range of Motion

There were no statistically significant differences between treatment groups for Global Joint Range of Motion Score, however there were improvements in elbow (p=0.0476) and shoulder joint mobility (p=0.0797) with weekly idursulfase compared to placebo.


Safety

Treatment with idursulfase was generally well-tolerated by patients in the trial. The most common adverse events observed were associated with the clinical manifestations of Hunter syndrome. Of the adverse events considered possibly related to idursulfase, infusion related reactions were the most common and were generally mild. There were two patient deaths during the study, both of which were considered unrelated to treatment with idursulfase. Of the 64 idursulfase-treated patients, 6 patients tested positive for IgG antibodies, and 2 patients tested positive for IgM antibodies at some time during the course of the study. No IgE antibodies were observed. No patient withdrew from the trial due to an adverse event considered related to idursulfase.

Proposed acquisition of Transkaryotic Therapies Inc.

Shire Pharmaceuticals Group plc announced July 27,2005, that the proposed acquisition of Transkaryotic Therapies, Inc. (“TKT”) was approved by Shire’s shareholders on July 27, 2005. The acquisition is now expected to complete on July 28, 2005.


Shire expects to pay approximately $1.6bn or $37 per common share in cash as consideration for the TKT shares in accordance with the terms of the acquisition.


Shire Chief Executive, Matthew Emmens, commented: “This is great news for Shire and TKT. This acquisition delivers on our strategy and brings a new drug development platform and expertise within a specialty area as well as further expansion into the European markets. We expect that this move will broaden our revenue base while continuing to grow our profits and further build our pipeline in a relatively low risk area of Enzyme Replacement Therapy.


“TKT transition will start immediately and David Pendergast will join our senior management team. We look forward to working with our new colleagues on the development and commercialization of their existing pipeline. The next important milestones this year are; the filing of I2S with the US Food and Drug Administration expected before the end of this year, as well as the publication of phase 1 clinical data for GA-GCB, a treatment for Gaucher’s disease.


“As previously stated, this acquisition is expected to significantly enhance Shire’s sales and EPS growth beyond 2007 and sustain Shire’s consistent operating margin performance.”


Chief Executive Officer of TKT, David Pendergast, Ph.D., said: “This is a tremendous opportunity for our business and our employees. We look forward to advancing our pipeline with the added expertise and resources that Shire brings to us. It is also great news for patients suffering from rare genetic disorders as it will enable us to introduce effective, life saving treatments that can make such a difference to their lives.”

TKT Reports Positive Top-Line Results of Hunter Syndrome Pivotal Trial

Primary Endpoint Achieves Statistical Significance

Transkaryotic Therapies, Inc. announced June 20, 2005 positive top-line results from the company's pivotal Phase III clinical trial evaluating its investigational human enzyme replacement therapy, iduronate-2-sulfatase (I2S), for the treatment of patients with Hunter syndrome. Hunter syndrome, also known as MPS II, is a rare, life-threatening genetic disorder with no available treatment. In the trial, patients who received 0.5 mg/kg of I2S on a weekly basis showed a statistically significant improvement in the primary efficacy endpoint (p=0.0049) compared to patients receiving placebo. Based on these results, TKT expects to file for regulatory approval of I2S in both the United States and Europe in the fourth quarter of 2005.

The primary efficacy endpoint of the trial, also referred to as the AIM study ("Assessment of I2S in MPS II") was a composite endpoint of two clinical measures previously used to assess clinical benefit in MPS disorders - forced vital capacity and six-minute walk test. The mean improvement from baseline to week 53 in percent predicted forced vital capacity was 3.4% in patients receiving I2S compared to 0.8% in patients receiving placebo. The mean increase from baseline to week 53 in the distance walked by patients receiving I2S was 44 meters as compared to 7 meters in the placebo group.

Joseph Muenzer, M.D., Ph.D., of the University of North Carolina at Chapel Hill, an internationally recognized leader in the diagnosis and treatment of MPS disorders and the lead investigator of the AIM study said, "These findings are very encouraging for the medical and patient communities as we believe enzyme replacement therapy can bring new hope for patients and families addressing many of the symptoms associated with Hunter syndrome."

Treatment with I2S was generally well-tolerated by patients in the trial. The most common adverse events observed were associated with the clinical manifestations of Hunter syndrome. Of the adverse events considered possibly related to I2S, infusion related reactions were the most common and were generally mild. No patient withdrew from the trial due to an adverse event considered related to I2S.

"We are extremely excited about the outcome of the study. In addition, we are very thankful to all the patients and their families who participated in this one year trial. Their commitment to this program was instrumental in generating the data which we believe will support regulatory approval of I2S," said Kip Martha, M.D., Senior Vice President and Chief Medical Officer of TKT.

TKT expects full data will be presented at a medical meeting in the autumn of 2005.

Trial Design

The AIM study was a Phase III double-blind, placebo-controlled clinical trial conducted at nine sites around the world, including the United States, the United Kingdom, Germany and Brazil. The primary goal of the study was to evaluate the safety and efficacy of 0.5 mg/kg of I2S administered weekly compared to placebo. Additionally, the trial evaluated 0.5 mg/kg of I2S every other week compared to placebo. Ninety-six patients with Hunter syndrome were randomized to one of three groups with each patient receiving a total of 52 infusions of either I2S, I2S alternating weekly with placebo, or placebo. Of the 96 who enrolled, 94 completed the study and they all elected to participate in the open-label extension study of I2S at a dose of 0.5 mg/kg weekly.

New Website Offers Comprehensive Information on Hunter Syndrome

Transkaryotic Therapies, Inc announced March 28, 2005 the launch of a new educational website focused on Hunter syndrome. Hunter syndrome, also referred to as MPS II, is a rare disorder in a class referred to as mucopolysaccharidoses or MPS. The site, http://www.hunterpatients.com, is a resource center for the Hunter community to access information about the genetics, diagnosis and management of Hunter syndrome as well as information about the drug development process.

TKT recently completed a multinational Phase III clinical trial evaluating an investigational enzyme replacement therapy for the treatment of Hunter syndrome. Results of the study are expected to be announced in June 2005 and, if positive, the company will file for regulatory approval in the U.S. and Europe in the second half of 2005.

"As we continue to learn more about MPS disorders and as new treatments are being developed, we hope to improve awareness of these rare and often life-threatening disorders. Easy access to information is the best way for families and practitioners to stay informed about new developments in the area," said Joseph Muenzer, M.D., Ph.D., of the University of North Carolina at Chapel Hill, an internationally recognized leader in the diagnosis and treatment of MPS disorders and the lead investigator of TKT's Phase III trial. "The launch of this site marks an important step toward offering patients, families and healthcare providers access to important medical and educational information relating to Hunter syndrome."

The website provides a comprehensive overview of Hunter syndrome, including resources for patients and healthcare professionals, information on clinical trials and a patient outcomes survey, as well as the ability to stay informed as new information about Hunter syndrome becomes available on the site. In addition, TKT expects to update and expand the site on a regular basis.

BioMarin Announces U.S. Launch of Naglazyme for MPS VI

BioMarin Pharmaceutical Inc. announced June 21, 2005 that Naglazyme(TM) (galsulfase) is now available in the United States as the first specific therapy approved for the treatment of individuals with mucopolysaccharidosis VI (MPS VI). Naglazyme was approved on May 31, 2005 by the U.S. Food and Drug Administration (FDA) and was shipped to distributors on Monday, June 20. The drug is being shipped to physicians this week. Naglazyme was developed by BioMarin and will be commercialized by the company's U.S.-based sales force. Naglazyme is indicated for patients with MPS VI. Naglazyme has been shown to improve walking and stair-climbing capacity.

"With the commercial launch of Naglazyme, individuals with MPS VI now have an approved treatment option that specifically addresses the underlying cause of this progressive and debilitating disease," stated Jean-Jacques Bienaime, Chief Executive Officer and Director of BioMarin. "Naglazyme is the second product developed by BioMarin to receive FDA approval and the first such product that we are commercializing on our own. We have prepared extensively for this moment and are optimistic that our preparation will result in a robust product launch."

In a separate release, BioMarin announced the appointment of Stephen Aselage to the position of Senior Vice President, Global Commercial Operations, effective July 1, 2005. BioMarin's commercial team includes four medical science liaisons who will be responsible for providing support to infusion centers and physicians who administer Naglazyme. The BioMarin sales force has mounted a disease awareness campaign targeted toward pediatricians and sub-specialists who are involved in the multi-disciplinary care of patients with MPS disorders to help drive new patient identification. Additionally, BioMarin has launched BioMarin Physician and Patient Support (BPPS), a free and confidential service established to assist patients and caregivers in their effort to receive insurance reimbursement for treatment with Naglazyme.

Naglazyme is administered once weekly via intravenous infusion and is dosed at 1 milligram of drug per kilogram of body weight. The annual cost of treatment will vary considerably according to each patient's weight.

ATU Program Under Way in France

In advance of product approval, BioMarin has received temporary use authorization (ATU) from regulatory authorities in France for named patient basis sales. Three patients who met certain selection criteria have begun to receive Naglazyme treatment. BioMarin expects to book revenue from these named patient basis sales and will continue to assist patients in Europe wherever possible prior to product approval in the European Union.

BioMarin Announces FDA Approval for Naglazyme

First Specific Therapy Approved for the Treatment of MPS VI

BioMarin Pharmaceutical Inc. announced June 1, 2005 that the U.S. Food and Drug Administration (FDA) has granted marketing approval for Naglazyme(TM) (galsulfase), the first specific therapy approved for the treatment of mucopolysaccharidosis VI (MPS VI). As the first drug ever approved for MPS VI, Naglazyme has been granted orphan drug status in the United States, which confers seven years of market exclusivity. BioMarin plans to launch Naglazyme in the United States in approximately 30 days. As post-marketing clinical commitments, BioMarin has agreed with the FDA to evaluate the effect of Naglazyme treatment on skeletal dysplasia in patients under the age of 1 and to maintain a clinical surveillance program to monitor patients on commercial therapy; no extension study of Phase 3 patients was required.

Clinical trials have demonstrated that Naglazyme provides clinically important benefits for MPS VI patients, specifically, improved endurance as demonstrated by the 12-minute walk test and 3-minute stair climb. Naglazyme reduced the excess carbohydrates (glycosaminoglycans, or 'GAGs') that are excreted in the urine of patients with MPS VI, an indication of enzymatic bioactivity.

"I have observed the positive effect that enzyme replacement therapy with Naglazyme can have on MPS VI patients, and I am very pleased that it will soon be made commercially available to those who need it," stated Paul Harmatz, M.D., Associate Director of the Pediatric Clinical Research Center at Children's Hospital & Research Center at Oakland, California, and Principal Investigator of the Phase 3 clinical trial of Naglazyme. "With Naglazyme now approved, physicians, for the first time, have a therapeutic to treat the underlying cause of MPS VI, increasing their ability to provide better care for MPS VI patients with this life-threatening disease."

"The approval of Naglazyme is a significant milestone for those whose life has been affected by MPS VI and for BioMarin," stated Jean-Jacques Bienaime, Chief Executive Officer of BioMarin. "The disease burden of MPS VI is enormous for patients, families and physicians. Naglazyme holds a very real possibility for making MPS VI a more manageable disease." Mr. Bienaime continued, "BioMarin developed Naglazyme on its own and now, with our U.S.- based sales force in place, we are ready to bring it to market. Our efforts to identify individuals with MPS VI in the years leading up to this day have positioned us to rapidly get patients on therapy come product launch. I would like to thank the individuals with MPS VI and their families and physicians as well as BioMarin employees for their years of hard work and dedication toward making Naglazyme for MPS VI a reality."

An application to market Naglazyme is currently pending in the European Union. BioMarin expects to receive an opinion from the European Commission in the fourth quarter of 2005, and if positive, final approval in early 2006.

Phase 3 Clinical Trial and Extension Study Results

BioMarin completed a 24-week, Phase 3, multi-center, double-blind, placebo-controlled trial involving 39 patients. Patients were randomized on a one-to-one basis into a Naglazyme treatment group or a placebo control group and received a weekly intravenous infusion of either 1.0 mg/kg of Naglazyme or placebo solution. During the 24-week period, 19 patients received weekly intravenous infusions of Naglazyme and 20 patients received weekly placebo infusions. One patient in the placebo group dropped out of the trial for reasons unrelated to treatment. All 38 patients who completed the trial elected to receive Naglazyme in an ongoing open-label extension study.

Efficacy Data

After 24 weeks of treatment, patients receiving Naglazyme demonstrated a statistically significant improvement (p=0.025) in endurance compared to patients receiving placebo as measured by the change relative to baseline in the distance walked in 12 minutes. The Naglazyme-treated group showed greater mean increase in distance walked in 12 minutes compared to the placebo group. The model-derived mean difference measured as a change from baseline between patients receiving Naglazyme and patients receiving placebo after 24 weeks was 92 +/- 40 meters. Following an additional 24 weeks of treatment with Naglazyme in the extension study, for a total of 48 weeks, patients demonstrated further improvement in endurance as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, patients receiving Naglazyme since week one of the trial improved their mean walk distance an additional 36 +/- 97 meters.

After 24 weeks of treatment, patients receiving Naglazyme demonstrated an improvement (p=0.053) in stair-climbing ability compared to patients receiving placebo as measured by the change relative to baseline in the number of stairs climbed per minute. The Naglazyme-treated group showed greater mean increase in the rate of stairs climbed in three minutes compared to the placebo group. The model-derived mean difference measured as a change from baseline between patients receiving Naglazyme and patients receiving placebo after 24 weeks was 5.7 +/- 2.9 stairs per minute. Following an additional 24 weeks of treatment with Naglazyme in the extension study, from week 24 to week 48, patients receiving Naglazyme since week one of the trial improved their mean number of stairs climbed per minute by an additional 3 +/- 7 stairs.

After 24 weeks of treatment, patients receiving Naglazyme experienced a statistically significant reduction (p<0.001) of GAGs excreted in the urine, compared to patients receiving placebo. The average urinary GAG reduction in patients receiving Naglazyme after 24 weeks was 75.5 percent. This initial reduction in urinary GAG levels was maintained following an additional 24 weeks of treatment in the extension study.

While in the extension study, patients who receive placebo solution during the initial 24-week trial demonstrated an improvement in endurance following 24 weeks of treatment with Naglazyme as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, the original placebo group demonstrated a mean increase of 65 meters relative to week 24 values. These patients also demonstrated an average improvement in stair-climbing ability as measured by stairs climbed in three minutes, relative to baseline, of 5.7 stairs per minute following 24 weeks of treatment with Naglazyme. Additionally, patients initially receiving placebo demonstrated a reduction in urinary GAG levels following 24 weeks of treatment with Naglazyme comparable to that observed for those treated in the initial 24-week, double-blind portion of the trial.

Safety Data

Data from the Phase 3 clinical trial and extension study indicate that Naglazyme was generally safe. The most common adverse events observed in clinical trials in Naglazyme-treated patients were headache, fever, arthralgia, vomiting, upper respiratory infections, abdominal pain, diarrhea, ear pain, cough, and otitis media. Over 95 percent of the infusion-related adverse events were considered mild or moderate and were easily managed. Infusion-related adverse events commonly included fever, chills/rigors, headache, rash, and mild to moderate urticaria. Severe reactions included angioneurotic edema, hypotension, dyspnea, bronchospasm, respiratory distress, apnea, and urticaria. No patients discontinued Naglazyme infusions for adverse events and all patients that completed the double-blind portion of the trial continue to receive weekly infusions of Naglazyme. Nearly all patients developed antibodies as a result of treatment, but the level of the immune response did not correlate with adverse events or impact the improvements experienced in endurance. Evaluation of airway patency should be considered prior to the initiation of treatment. Consideration to delay Naglazyme infusion should be given when treating patients who present with an acute febrile or respiratory illness.

BioMarin's Phase 3 Extension Study of rhASB in MPS VI Demonstrates Additional Improvements in Endurance

Further Improvements in Patients Receiving rhASB and Significant Improvements in Patients Previously Receiving Placebo

BioMarin Pharmaceutical Inc. March 9 2005 announced positive results from the Phase 3 extension study of rhASB (galsulfase), the company's investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). Data from the study demonstrate that patients who received rhASB for an additional 24 weeks, for a total of 48 weeks, continued to experience improved endurance. Patients who initially received placebo and then received rhASB for 24 weeks also experienced improved endurance. The data were presented by Stuart Swiedler, M.D., Ph.D., Senior Vice President of Clinical Affairs at BioMarin, at the annual meeting of the Society for Inherited Metabolic Diseases held in Pacific Grove, California.

Dr. Swiedler stated, "We are pleased to see continued benefit experienced by MPS VI patients receiving extended treatment with rhASB for MPS VI. The Phase 3 extension data further confirm the positive safety and efficacy profile of rhASB we have observed since the initiation of the clinical program, and we are working to make this therapy commercially available to individuals with MPS VI in the United States in the second half of the year."

Phase 3 Extension Study Design

All 38 patients who completed the initial 24-week, Phase 3, multi-center, double-blind, placebo-controlled trial were enrolled in the open-label extension study to further evaluate the safety and efficacy of rhASB. Patients who received rhASB during the initial 24-week, placebo-controlled portion of the trial continued to receive weekly 1.0 mg/kg infusions of rhASB in the extension study. Patients who initially received placebo during the placebo-controlled portion of the trial received 1.0 mg/kg of rhASB via weekly infusion during the extension study. Patients were evaluated at pre-defined, six-week intervals to assess changes in primary and secondary efficacy endpoints and the safety and tolerability of weekly rhASB infusions. Results of the study for the groups are summarized below:

Results from Patients Receiving 48 Weeks of rhASB

Patients demonstrated further improvement in endurance following an additional 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean walk distance an additional 36 meters for a total of 145 meters for the 48-week period.
Patients demonstrated a further improvement in endurance following 48 weeks of treatment with rhASB as measured by the number of stairs climbed in three minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean number of stairs climbed per minute by an additional 2.9 stairs for a total of a 10.4 stairs-per-minute improvement for the 48-week period.
The initial reduction in urinary glycosaminoglycan (GAG) levels, an in vivo measure of enzyme activity, was maintained from week 24 to week 48. Urinary GAG levels were reduced by 75.5 percent during the initial 24-week period.
Results from Patients Receiving 24 Weeks of rhASB

Patients initially receiving placebo demonstrated improvements in endurance following 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, the original placebo group demonstrated a mean increase of 65 meters relative to week 24 values.
Patients initially receiving placebo solution demonstrated an average improvement in endurance as measured by stairs climbed in three minutes, relative to baseline, of 5.7 stairs per minute following 24 weeks of treatment with rhASB.
Patients initially receiving placebo demonstrated a reduction in urinary GAG levels following 24 weeks of treatment with rhASB comparable to that observed for those treated in the initial 24-week, double-blind portion of the trial (p<0.001).
Data indicate that rhASB was generally safe and well-tolerated. The majority of adverse events reflected the underlying disease state or occurred during drug infusion. Over 95 percent of the infusion-related adverse events were considered mild or moderate and were easily managed. No patients discontinued rhASB infusions for adverse events and all patients that completed the double-blind portion of the trial continue to receive weekly infusions of rhASB. Nearly all patients developed antibodies as a result of treatment, but the level of the immune response did not correlate with adverse events or impact the improvements experienced in endurance.

FDA Accepts and Grants Six-Month Review for BioMarin's Marketing Application for rhASB for MPS VI PDUFA Date Set for May 31, 2005

BioMarin Pharmaceutical Inc. announced Feb. 1, 2005 that the U.S. Food and Drug Administration (FDA) has accepted for filing and assigned six-month review to the Biologics License Application (BLA) for rhASB (galsulfase), the company's investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). The FDA will take action on the application, under the Prescription Drug User Fee Act (PDUFA), by May 31, 2005. A six-month review is typically granted to drugs that, if approved, would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious or life-threatening disease. The FDA previously granted rhASB orphan drug designation, a designation conferred upon investigational products for diseases that affect fewer 200,000 patients in the United States. Products with orphan drug designation that are the first to be approved for a specific indication have seven years market exclusivity within the United States. About rhASB rhASB is an investigational enzyme replacement therapy designed to address the underlying enzyme deficiency associated with MPS VI. If approved, rhASB could become the first drug therapy for the treatment of MPS VI.

BioMarin's Phase 3 Extension Study of rhASB in MPS VI Demonstrates Additional Improvements in Endurance

Further Improvements in Patients Receiving rhASB and Significant Improvements in Patients Previously Receiving Placebo BioMarin Pharmaceutical Inc. announced March 9th positive results from the Phase 3 extension study of rhASB (galsulfase), the company's investigational enzyme replacement therapy for the treatment of mucopolysaccharidosis VI (MPS VI). Data from the study demonstrate that patients who received rhASB for an additional 24 weeks, for a total of 48 weeks, continued to experience improved endurance. Patients who initially received placebo and then received rhASB for 24 weeks also experienced improved endurance. The data were presented by Stuart Swiedler, M.D., Ph.D., Senior Vice President of Clinical Affairs at BioMarin, at the annual meeting of the Society for Inherited Metabolic Diseases held in Pacific Grove, California. Dr. Swiedler stated, "We are pleased to see continued benefit experienced by MPS VI patients receiving extended treatment with rhASB for MPS VI. The Phase 3 extension data further confirm the positive safety and efficacy profile of rhASB we have observed since the initiation of the clinical program, and we are working to make this therapy commercially available to individuals with MPS VI in the United States in the second half of the year." Phase 3 Extension Study Design All 38 patients who completed the initial 24-week, Phase 3, multi-center, double-blind, placebo-controlled trial were enrolled in the open-label extension study to further evaluate the safety and efficacy of rhASB. Patients who received rhASB during the initial 24-week, placebo-controlled portion of the trial continued to receive weekly 1.0 mg/kg infusions of rhASB in the extension study. Patients who initially received placebo during the placebo-controlled portion of the trial received 1.0 mg/kg of rhASB via weekly infusion during the extension study. Patients were evaluated at pre-defined, six-week intervals to assess changes in primary and secondary efficacy endpoints and the safety and tolerability of weekly rhASB infusions. Results of the study for the groups are summarized below: Results from Patients Receiving 48 Weeks of rhASB -- Patients demonstrated further improvement in endurance following an additional 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean walk distance an additional 36 meters for a total of 145 meters for the 48-week period. -- Patients demonstrated a further improvement in endurance following 48 weeks of treatment with rhASB as measured by the number of stairs climbed in three minutes, relative to baseline. From week 24 to week 48, patients receiving rhASB since week one of the trial improved their mean number of stairs climbed per minute by an additional 2.9 stairs for a total of a 10.4 stairs-per-minute improvement for the 48-week period. -- The initial reduction in urinary glycosaminoglycan (GAG) levels, an in vivo measure of enzyme activity, was maintained from week 24 to week 48. Urinary GAG levels were reduced by 75.5 percent during the initial 24-week period. Results from Patients Receiving 24 Weeks of rhASB -- Patients initially receiving placebo demonstrated improvements in endurance following 24 weeks of treatment with rhASB as measured by the change in distance walked in 12 minutes, relative to baseline. From week 24 to week 48, the original placebo group demonstrated a mean increase of 65 meters relative to week 24 values. -- Patients initially receiving placebo solution demonstrated an average improvement in endurance as measured by stairs climbed in three minutes, relative to baseline, of 5.7 stairs per minute following 24 weeks of treatment with rhASB. -- Patients initially receiving placebo demonstrated a reduction in urinary GAG levels following 24 weeks of treatment with rhASB comparable to that observed for those treated in the initial 24-week, double-blind portion of the trial (p<0.001). Data indicate that rhASB was generally safe and well-tolerated. The majority of adverse events reflected the underlying disease state or occurred during drug infusion. Over 95 percent of the infusion-related adverse events were considered mild or moderate and were easily managed. No patients discontinued rhASB infusions for adverse events and all patients that completed the double- blind portion of the trial continue to receive weekly infusions of rhASB. Nearly all patients developed antibodies as a result of treatment, but the level of the immune response did not correlate with adverse events or impact the improvements experienced in endurance.

Genzyme Sues to Halt TKT Gaucher Trial TKT to Defend Patent Suit in Israel

Transkaryotic Therapies, Inc. (TKT) announced Jan. 24, 2005 that Genzyme Corporation has filed suit against TKT in the District Court of Tel-Aviv-Jaffa but not yet formerly served process on TKT. The suit claims that TKT's Phase I/II clinical trial evaluating its investigational Gene-Activated(R) glucocerebrosidase (GA-GCB) for the treatment of Gaucher disease infringes one or more claims of Israeli Patent No. 100,715. In addition, Genzyme filed a motion for preliminary injunction, including a request for an ex parte hearing and relief on the merits, to immediately seize and destroy all GA-GCB being used to treat patients in TKT's ongoing clinical trial and to prevent the company from submitting data generated from the clinical trial to regulatory agencies. The judge has already rejected Genzyme's request for ex parte relief. "We believe Genzyme's efforts to try and disrupt our ongoing clinical development of GA-GCB are an improper attempt to extend its monopoly in the area of Gaucher disease," said Kerry A. Flynn, Vice President of Intellectual Property and Licensing at TKT. "We do not believe we infringe any valid claim or that there is a reasonable likelihood that this unprecedented tactic will interrupt our clinical trial. We intend to honor our commitment to continue treating our Gaucher patients with GA-GCB." TKT is conducting an open-label Phase I/II study to evaluate the safety and clinical activity of GA-GCB. The study enrolled twelve patients with Type I Gaucher disease from several countries. TKT expects to report top-line data from this study in the second half of 2005. Gaucher disease is the most common of the inherited lysosomal storage diseases and is caused by a deficiency of the enzyme glucocerebrosidase. As a result of this deficiency, certain lipids accumulate in specific cells of the liver, spleen, and bone marrow causing significant clinical symptoms in the patient, including enlargement of the liver and spleen, hematologic abnormalities, and bone disease.

Genzyme Files for European Approval of Myozyme® For Treatment of Pompe Disease

Genzyme Corp. announced 20 December 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.

Genzyme, AGTC Announce Gene Therapy Collaboration

Genzyme Corporation and Applied Genetic Technologies (AGTC), a private development-stage biotechnology company, announced 6th December 2004 that they have entered into a research collaboration to jointly develop novel therapeutics involving gene therapy. Through the collaboration, Genzyme gains access to AGTC's extensive expertise using Adeno-Associated Virus (AAV) vectors to deliver genes to patients, including access to AGTC's novel high-yield manufacturing capabilities for AAV vectors. These vectors may have therapeutic advantages in several disease areas where Genzyme has active preclinical development programs, including lysosomal storage disorders, cardiovascular disease, central nervous system disorders, immune-mediated disorders, and others. Genzyme brings to the collaboration more than a decade of experience with gene therapy, involving multiple clinical trials in cardiovascular disease, oncology, and cystic fibrosis. Financial terms were not disclosed. "We are delighted to collaborate with an established biotechnology leader like Genzyme, which has contributed heavily to many advances in our understanding of gene therapy," said Sue Washer, CEO of AGTC. "This agreement is an important validation of AGTC's technology, and will position us to build on our early work in a number of therapeutic areas and enable us to bring products to market more efficiently." "Our work with AGTC will bring Genzyme an impressive technology platform, which includes a scalable, highly productive manufacturing capability with the potential to support future clinical trials and product development," said Sam Wadsworth, vice president, Translational Research at Genzyme. AGTC has licensed a significant portion of its intellectual property from the University of Florida where researchers originated this ground-breaking work in gene therapy. AGTC is developing novel therapeutics for patients with unmet medical needs utilizing the non-pathogenic adeno-associated virus. AGTC's first product candidate is a treatment for Alpha One Antitrypsin Deficiency, an inherited form of emphysema; Phase I trials are underway with a potential product launch in early 2009. AGTC's investors include Interwest Partners (Menlo Park, California), Intersouth Partners (Durham, North Carolina), MedImmune Ventures (Gaithersburg, Maryland) and Skyline Ventures (Palo Alto, California). The company is located in Gainesville, Florida in the University of Florida's business development park. 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. Genzyme's commitment to innovation continues today with research into novel approaches to cancer, heart disease, and other areas of unmet medical need. More than 7,000 Genzyme employees in offices around the globe serve patients in over 80 countries.

TKTs I2S for Hunter Syndrome Receives Office of Orphan Products Grant

CAMBRIDGE, Mass., Sept. 28 /PRNewswire-FirstCall/ -- Transkaryotic Therapies, Inc. (Nasdaq: TKTX) today announced that it has received a Development Grant from the FDA's Office of Orphan Products Development (OOPD) for iduronate-2-sulfatase (I2S), TKT's investigational enzyme replacement therapy for the treatment of Hunter syndrome, also known as MPS II, a rare, fatal disease. The $300,000 grant will pay for some costs of the company's ongoing pivotal trial. "We are grateful for this recognition of the importance of our efforts to develop I2S as a potential treatment for Hunter syndrome. We fully support the FDA's mission to encourage clinical development of products for rare diseases and to put agency resources behind these development efforts," said Michael J. Astrue, President and Chief Executive Officer of TKT. Since 1989, approximately 36 products supported by OOPD grants have received marketing approval by the U.S. Food and Drug Administration. Clinical studies conducted under an Investigational New Drug application for a rare disease qualify for consideration by the program. Grants of this size are typically awarded to drugs in Phase III clinical trials. The I2S pivotal trial, referred to as the AIM (Assessment of I2S in MPS II) study, is a fully enrolled trial designed to evaluate safety and efficacy of weekly and every-other week infusions of I2S administered at a dose of 0.5 mg/kg. Patients will receive a total of fifty-two infusions of either I2S (patients randomized to the weekly dosing regimen), I2S alternating with placebo (patients randomized to the every other week regimen), or placebo. The AIM study is a twelve-month, randomized, double-blind, placebo-controlled trial being conducted at nine sites around the world. The primary efficacy endpoint in the trial is a single composite variable which combines two clinical measurements: forced vital capacity as a measure of respiratory function and the six-minute walk test as a measure of functional capacity. Additional efficacy endpoints include measurements of joint range of motion and combined liver/spleen size. TKT expects top-line results from the AIM study in the second quarter of 2005 and, if positive, the company expects to submit applications for marketing approval in both the United States and Europe in the second half of 2005.

TKT Receives Fast Track Designation For Iduronate-2-Sulfatase for Hunter Syndrome.

CAMBRIDGE, Mass., July 15 /PRNewswire-FirstCall/ -- Transkaryotic Therapies, Inc. (Nasdaq: TKTX) today announced that it has received fast track designation from the U.S. Food and Drug Administration (FDA) for iduronate-2- sulfatase (I2S) to treat Hunter syndrome (MPS II). TKT commenced a pivotal study with I2S in September 2003. The study, referred to as AIM (Assessment of Iduronate-2-sulfatase in MPS II) is a twelve-month, randomized, double-blind, placebo-controlled trial evaluating I2S in 96 patients. TKT expects top-line results from the AIM study in the second quarter of 2005 and, if positive, the company expects to submit applications for marketing approval in both the United States and Europe in the second half of 2005. "We are pleased that the FDA has given I2S this important designation," said Michael J. Astrue, President and Chief Executive Officer of TKT. "We are committed to bringing this treatment to patients as quickly as possible."

About Fast Track Designation

Under the FDA Modernization Act of 1997, fast track regulations are designed to facilitate the development of products to treat serious or life- threatening diseases where an unmet medical need exists. Fast track regulations are also designed to expedite the review process for designated products, including the potential for companies to submit marketing applications on a rolling basis.

TKT to Present Research on Intrathecal Delivery of I2S for Hunter Syndrome at ASHG New Data on Lysosomal Storage Disease Programs to be Presented

CAMBRIDGE, Mass., Sept. 20/PRNewswire-FirstCall/ -- Transkaryotic Therapies, Inc. (Nasdaq: TKTX) today announced that its research findings evaluating intrathecal delivery of iduronate-2-sulfatase (I2S) in an animal model will be presented at the American Society of Human Genetics 54th Annual Meeting in Toronto. I2S is TKT’s investigational enzyme replacement therapy being developed for the treatment of Hunter syndrome, also referred to as MPS II, a rare and often fatal disease. These research findings will be presented by Dr. Justin Lamsa of TKT at a poster session from 5:00 – 7:00 p.m. on Thursday, October 28, 2004. Recently, TKT made the decision to advance a program evaluating delivery of I2S directly into the central nervous system into preclinical development. The company expects to file an Investigational New Drug Application to commence human clinical trials of its I2S CNS program in the first half of 2006. “As part of our ongoing efforts to broadly serve patients suffering from rare diseases, we are committed to understanding how best to administer treatments targeting the central nervous system. Our hope is that intrathecal injection or other delivery methods may be feasible in treating patients affected with Hunter syndrome who develop central nervous system complications,” said Michael Heartlein, Ph.D., Vice President, Research at TKT.

.