Shire Shire Pharmaceutical, formerly known as Transkaryotic Therapies, Inc. (TKT) is a biopharmaceutical company located in Cambridge, MA, with a major focus on developing primarily products for the treatment of rare diseases. July 24, 2006: Shire announced today that the FDA has granted marketing approval for ELAPRASE, a human enzyme replacement therapy for the treatment of Hunter syndrome, also known as Mucopolysaccharidosis II (MPS II) Press Release Shire Press Release May 17, 2006 17 May 2006 - Cambridge, MA US and Basingstoke, UK – May 17, 2006 -- Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announces that the Food and Drug Administration (FDA) has extended by 90 days the review period for the biologics license application (BLA) for ELAPRASETM (idursulfase). This extension will allow the FDA additional time to review data and analyses they recently requested during label discussions. Therefore, the FDA advised us at close of US business yesterday that the new action date for the application is August 24, 2006. "Shire will continue to work closely with the FDA during this brief extension of the ELAPRASE BLA review and through this cooperative effort we expect that ELAPRASE will be approved and launched by the third quarter 2006," said Matthew Emmens, Chief Executive Officer of Shire. "There is no existing treatment for patients with Hunter syndrome and Shire is confident that the FDA recognizes the importance of making ELAPRASE available to these patients." The US BLA for ELAPRASE was submitted in November 2005 and was granted priority review, requiring the FDA to take action within six months. A marketing authorization application for ELAPRASE has been submitted to the European Medicines Agency, and Shire expects a response on that application before the end of the year. ELAPRASE has been developed for the treatment of Hunter syndrome, a serious genetic disorder, mainly affecting males, that interferes with the body's ability to break down and recycle specific chemicals called mucopolysaccharides, also known as glycosaminoglycans or GAG. Hunter syndrome is one of several related lysosomal storage diseases. TKT's 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 Offers Support for MPS II TKT MPS II families to contact Leanne Torrie, RN, Patient Services Manager at (617) 613-4499 or ltorrie@tktx.com. By contacting Leanne, TKT will be able to: Help you remain informed about TKT initiatives Begin to locate physicians in your area that are specialized in the care of MPS patients, or provide further education to your current physicians Assist with healthcare insurance questions TKT Reports Positive Results of MPS II Clinical Trial.... Transkaryotic Therapies, Inc. announced in a 6/20/2005 press release the 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.The National MPS Society extends our congratulations to everyone who was involved with this extensive clinical trial, including TKT, the study centers, the investigators, and especially the individuals with MPS II and their families, who have been a part of the MPS II clinical trials. Because of their commitment, we are hopeful that all individuals with MPS II will have the opportunity for enzyme replacement therapy. TKT Receives Fast Track Designation For Iduronate-2-Sulfatase for Hunter Syndrome CAMBRIDGE, Mass., July 15, 2004 Transkaryotic Therapies, Inc. 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. Development of CNS targeted treatments for MPS II and MPS III Please read this informative letter from Mike Astrue, President and CEO, at TKT, regarding TKT's continuing commitment to developing therapies for rare genetic diseases, including Hunter syndrome (MPS II) and hopefully soon Sanfilippo syndrome (MPS III). Click here for Mike's Letter.