Shire Pharmaceuticals Group plc Release: Data From Two Pivotal Phase III Studies Presented During Digestive Disease Week (DDW) Show MMX Mesalamine (Mesavance(TM)) Induced Remission Of Ulcerative Colitis (UC)

LOS ANGELES, May 24 /PRNewswire/ -- Combined results of two pivotal phase III clinical studies (301 and 302) of a novel formulation of Multi-Matrix System(TM) (MMX) mesalamine, a medication currently under review by the FDA, Canadian, and EU regulatory agencies, were presented today during DDW at the Los Angeles Convention Center. The data demonstrated that MMX mesalamine induced remission in patients with active mild-to-moderate UC, and was generally well tolerated at once-daily and twice-daily dosing.

Analyses of the data revealed that MMX mesalamine induced remission of active mild-to-moderate UC in patients changed from other oral 5-ASA therapies and in patients who were 5-ASA naive. Both once-daily and twice-daily MMX mesalamine induced remission in patients with left-sided or extensive UC.

Mesalamine is used as a first-line treatment for mild-to-moderate UC. MMX mesalamine utilizes a novel proprietary MMX technology to provide the highest mesalamine dose per tablet (1.2 g). It also employs a gastro-resistant polymer to delay release of the active drug until it reaches the terminal ileum, and the MMX drug delivery technology is believed to extend delivery of 5-ASA consistently throughout the entire colon.

Studies 301 and 302 were prospective, randomized, multicenter, double-blind, placebo-controlled, phase III studies examining the efficacy and tolerability of MMX mesalamine in once-daily and twice-daily dosing. The data were combined for patients receiving MMX mesalamine 2.4 g/day (given once daily [QD; Study 302] or twice daily [BID; Study 301] combined n=172), MMX mesalamine 4.8 g/day (given QD [Studies 301 and 302] combined n=174) or placebo (combined n=171).

At week 8, a statistically significantly greater population of patients achieved remission in the MMX mesalamine 2.4 g/day group compared with the placebo group (37.2% vs. 17.5% [P<0.001]). A statistically significantly greater population of patients in the MMX mesalamine 4.8 g/day QD group also achieved remission compared with the placebo group (35.1% vs. 17.5% [P<0.001]).(1)

"These data show that this novel formulation of MMX mesalamine was generally well tolerated and induced remission in patients with active mild- to-moderate UC," said primary investigator Dr. William J. Sandborn, Inflammatory Bowel Disease Clinic, Mayo Clinic. "MMX mesalamine may improve patient compliance and overall treatment success."

Statistically significant results in patients with left-sided or extensive UC

A second analysis of the combined data examined the treatment responses in patients with left-sided or extensive UC. At week 8, a statistically significantly greater population of patients with left-sided UC receiving MMX mesalamine 2.4 g/day or 4.8 g/day achieved remission compared with placebo (37.2% [P<0.001] and 33.3% [P=0.006] vs. 18.6%, respectively). A statistically significantly greater population of patients with extensive UC receiving either 2.4 g/day or 4.8 g/day of MMX mesalamine achieved remission by week 8, compared with placebo (37.1% [P=0.034] and 42.9% [P=0.005] vs. 14.3%, respectively). No correlation between disease location and treatment activity was observed.(2)

"Nearly 80 percent of patients diagnosed with UC have left-sided disease, which affects the colon below the splenic flexure," said Dr. Michael A. Kamm, Department of Gastroenterology, St. Mark's Hospital, London, who is also involved with the studies. "The current 5-ASA treatments often require multiple daily oral dosing or enema administration, which may impact patient compliance. MMX mesalamine achieved its endpoint of induction of remission in these patients with a once- and twice-daily dosing."

MMX mesalamine was generally well tolerated

The most common adverse events reported in MMX mesalamine phase III studies were headache (4.5%) and flatulence (3.4%).

Patients who changed to MMX mesalamine achieved remission

The 301 and 302 studies also showed that significantly more patients who were taking prior low-dose oral 5-ASA (discontinued oral 5-ASA therapy [less than or equal to 2 g/day] less than or equal to 5 days prior to baseline) to MMX mesalamine 4.8 g/day achieved remission compared to placebo (37.5% [P<0.05] vs. 20.9%). A greater number of patients who changed to MMX mesalamine 2.4 g/day from their prior 5-ASA therapy also achieved remission compared to placebo (31.8%).

Significantly more patients who were 5-ASA naive (no prior oral 5-ASA or had discontinued oral 5-ASA therapy [less than or equal to 2 g/day] >5 days prior to baseline) and changed to MMX mesalamine 2.4 g/day or 4.8 g/day also achieved remission following either dose of MMX mesalamine compared with placebo (42.9% [P<0.001] and 33% [P<0.01] vs. 13.8%, respectively).(3)

"These combined data demonstrate that MMX mesalamine is an important advancement in the treatment of UC," Sandborn said. "This novel formulation was generally well tolerated, and offers UC patients a convenient dosing regimen that may help improve compliance."

Shire is continuing the development of MMX mesalamine. Shire has licensed from Giuliani S.p.A. the exclusive right to develop and commercialize MMX mesalamine in the US, Canada and Europe (excluding Italy). Giuliani S.p.A. retains the development and commercialization rights to MMX mesalamine in Italy.

About MMX Mesalamine (Mesavance)

MMX mesalamine is a novel, high-dose 5-aminosalicylic acid (5-ASA; mesalamine) in a delayed and extended release formulation (MMX) being studied for the induction of remission of active mild-to-moderate UC.

About Giuliani S.p.A.

Giuliani S.p.A., founded in 1889, is a privately owned specialty pharmaceutical company with headquarters in Milan, Italy. It develops new products with high unmet medical need and substantial market opportunity. Giuliani S.p.A. is focused on developing and marketing products for the treatment and management of gastrointestinal (ulcerative colitis and Crohn's disease), metabolic (food intolerance), and dermatological (hair loss) disorders.

About Shire plc

Shire's strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on central nervous system (CNS), gastrointestinal (GI), general products (GP), and human genetic therapies (HGT) -- all being areas in which Shire has a commercial presence. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.

Shire's focused strategy is to develop and market products for specialty physicians. This approach aims to deliver increased returns and lower risks. Shire's in-licensing and merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.

For further information on Shire, please visit the Company's website: http://www.shire.com.

"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included herein that are not historical facts are forwarding- looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire plc's results could be materially affected. The risks and uncertainties include, but are not limited to: risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to, the impact of those on Shire plc's Attention Deficit and Hyperactivity Disorder ("ADHD") franchise; patents, including but not limited to, legal challenges relating to Shire plc's ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (ADHD), SPD465 (ADHD), MESAVANCE(TM) (SPD476) (ulcerative colitis), ELAPRASE(TM) (I2S) (Hunter syndrome) and NRP104 (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire plc's ability to benefit from the acquisition of Transkaryotic Therapies Inc.; Shire plc's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire plc's and its predecessor registrant Shire Pharmaceuticals Group plc's filings with the US Securities and Exchange Commission, including Shire plc's Annual Report on Form 10-K for the year ended December 31, 2005.

About Digestive Disease Week (DDW)

DDW is the largest international gathering of physicians, researchers, and academics in the fields of gastroenterology, hepatology, endoscopy, and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 20-25, 2006, at the Los Angeles Convention Center. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine, and technology. For more information, visit http://www.ddw.org.

(1) Sandborn, W., et al. Combined data from two pivotal, randomized, placebo-controlled, phase III studies show that SPD476, a novel mesalamine formulation given once or twice daily, is effective for the induction of remission of mild-to-moderate ulcerative colitis. Presented at Digestive Disease Week, Los Angeles, CA, May 20-25, 2006. (2) Kamm, M., et al. SPD476, a novel formulation of 5-ASA given once or twice daily, is effective for the induction of remission of left-sided and extensive ulcerative colitis: an analysis of combined data from two pivotal, randomized, placebo-controlled phase III studies. Poster T1148 presented at Digestive Disease Week, Los Angeles, CA, May 20-25, 2006. (3) Sandborn, W., et al. SPD476, a novel, high-strength 5-ASA formulation induces remission of active, mild-to-moderate ulcerative colitis in subjects that are switched from low-dose oral 5-ASA therapy or are 5-ASA naive: an analysis of pooled data from two phase III studies. Poster T1139 presented at Digestive Disease Week, Los Angeles, CA, and May 20-25, 2006. Contact: May Baccari Office: 212-845-4279/cell: 253-230-3789 Email: may.baccari@eurorscg.com

Shire plc

CONTACT: May Baccari, +1-212-845-4279, or cell: +1-253-230-3789,may.baccari@eurorscg.com, for Shire plc

Web site: http://www.shire.com/http://www.ddw.org/