News Release

LIALDA (TM) demonstrates prolonged release of mesalamine

In vitro study used a simulated colon

Peer-Reviewed Publication

Shire plc

Philadelphia, PA – October 17, 2007 – According to a study using a dynamic in vitro gastrointestinal tract system, Shire plc's (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) ulcerative colitis drug LIALDA™ (mesalamine) demonstrated a delivery system where the majority of the drug’s active ingredient, 5-aminosalicyclic acid (5-ASA), is released over a prolonged period in the simulated colon. The colon is the site of inflammation in ulcerative colitis. In this in vitro model, after the LIALDA tablet passed through the simulated stomach, small intestine and colon compartments, the majority of 5-ASA within each tablet was released in the simulated colon (nearly 90 percent in simulated fasted state and 81 percent in the simulated fed state). Less than 1 percent of the 5-ASA was released from the tablet in the simulated stomach and small intestine. The study used the TNO Gastrointestinal Model, or TIM, which simulates a human stomach, small intestine and colon. The findings were published in the July/August issue of Advances in Therapy.

“To our knowledge, traditional, delayed-release 5-ASA formulations have no mechanism for prolonging the release of 5-ASA once the tablet enters the colon, which may lead to the majority of 5-ASA being released immediately upon entering the colon instead of in the areas most likely to be inflamed,” said lead study investigator and Senior Director of Pharmaceutical Sciences at Shire, Srini Tenjarla, PhD. “Using the TIM system, a well-known and widely used system that mimics the fate of ingested products in the human adult GI tract, we were able to demonstrate that LIALDA tablets provide maximum release of 5-ASA in a prolonged manner, with minimal formulation disintegration and release in the simulated small intestine.

The TIM system allowed us to observe that after exposure to the simulated stomach and small intestine and immediately prior to being introduced into the simulated colon compartment, the LIALDA tablets had a swollen appearance and the first appearance of cracks on the outer tablet coating. This demonstrates that very little drug is released in the simulated stomach and small intestine and suggests that the majority of mesalamine is released in the simulated colon,” said Dr. Tenjarla.

LIALDA with Multi Matrix System (MMX®) Technology combines a pH-dependent gastro-resistant coating, which delays the release of the medication to the colon, with a tablet core containing mesalamine with hydrophilic and lipophilic excipients. LIALDA is the only ulcerative colitis treatment that utilizes MMX Technology.

In two pivotal phase III clinical studies, LIALDA was shown to be superior to placebo in inducing remission and treating the symptoms of mild-to-moderate UC. LIALDA was generally well tolerated.

About the Study

The release kinetics of 5-ASA from LIALDA were assessed using the TIM system that simulated the physiologic conditions in the adult human gastrointestinal tract under standardized fed and fasted conditions. In the analysis, the LIALDA 1.2g tablet was introduced to the TIM system, along with a mixture of artificial saliva and tap water (fasted state) or a mixture of artificial saliva and the standard FDA high-fat breakfast (fed state). The total intake was always 200g and all experiments were performed in duplicate.

After all samples were collected, a validated high-performance liquid chromatography method with ultra-violet detection was used to quantify levels of 5-ASA in the samples. Samples were analyzed using a Phenomenex Aqua 5 3µm column (150mm by 3mm inner diameter) at 40 degrees Celsius (excitation/emission wavelength 315/430nm).

The analysis found that during passage through the gastric and small intestine compartments of TIM, on average less than one percent (0.25 percent in fasted state and 0.84 percent in fed state) of the 5-ASA was released from LIALDA. In contrast, during passage through the colon compartments of TIM, 78.01 percent of the 5-ASA was released from LIALDA in a fasted state and 68.49 percent in fed state. The remaining 11.64 percent (fasted state) and 13 percent (fed state) were recovered in the simulated colon residue. The apparent difference in recovery rates is minor in both simulated fasted and fed states as the results still show the continuing presence of high concentrations of 5-ASA in the colon. After an initial lag of about 2–3 hours, 5-ASA was released in the simulated colon consistently over approximately 20 hours. Analysis of the rate of 5-ASA release showed an initial linear increase that peaked at 67.5mg/hour within 5–6 hours in the simulated fed state and at 73.3mg/hour within 6–8 hours in the simulated fasted state.

Clinical relevance of in vitro data is unknown.

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About LIALDA

LIALDA is part of a drug class called aminosalicylates, which contain 5-aminosalicyclic acid (5-ASA). 5-ASA is a well-established drug of choice and often a first-line treatment for ulcerative colitis. LIALDA is indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. The safety and efficacy of LIALDA have been established for up to eight weeks. LIALDA is the first new formulation in this class to be approved since 2000.

Shire has licensed from Giuliani SpA the exclusive rights to develop and commercialize LIALDA in the U.S., Canada, Europe -- known as MEZAVANT™ -- (excluding Italy) and the Pacific Rim. Giuliani SpA retains the development and commercialization rights in Italy. Cosmo Pharmaceuticals SpA, Milan, developed the MMX Technology.

For more information about LIALDA and for Full Prescribing Information, please visit www.LIALDA.com.

Important Safety Information

LIALDA tablets are indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. Safety and effectiveness of LIALDA beyond eight weeks have not been established.

LIALDA is contraindicated in patients with hypersensitivity to salicylates (including mesalamine) or to any of the components of LIALDA. Caution should be exercised when treating patients with pyloric stenosis or those allergic to sulfasalazine. Mesalamine has been associated with an acute intolerance syndrome (three percent of patients in clinical trials with mesalamine or sulfasalazine) that may be difficult to distinguish from a flare of inflammatory bowel disease. If acute intolerance syndrome is suspected, prompt withdrawal is required. Mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported.

Reports of renal impairment have been associated with mesalamine medications. In patients with renal impairment, caution should be exercised, and LIALDA should be used only if the benefits outweigh the risks. No information is available for patients with hepatic impairment.

LIALDA is generally well tolerated. The majority of adverse events in the double-blind, placebo-controlled trials were mild or moderate in severity. In clinical trials (N=535), the most common treatment-related adverse events with LIALDA 2.4g/day, 4.8g/day and placebo were headache (5.6 percent, 3.4 percent and 0.6 percent, respectively) and flatulence (four percent, 2.8 percent and 2.8 percent, respectively). Pancreatitis occurred in less than one percent of patients during clinical trials and resulted in discontinuation of therapy with LIALDA.

SHIRE PLC

Shire’s strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit and hyperactivity disorder (ADHD), human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire’s in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe. Shire believes that a carefully selected portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.

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

For media inquiries please contact:

Media:
Ashleigh Duchene (GolinHarris) +1 312 729 4428
Matthew Cabrey (Shire) +1 484 595 8248

GIULIANI SpA

Giuliani SpA, founded in 1889, is a privately owned specialty biopharmaceutical company strategically focused in gastroenterology and dermatology. It is currently marketing proprietary products for the treatment and management of ulcerative colitis, Crohn’s disease, food intolerances and dermatological disorders. Giuliani’s R&D pipeline includes new chemical entities and biotechnological products targeted to treat inflammatory and autoimmune diseases.

COSMO Pharmaceuticals SpA

Cosmo is a speciality pharma company that aims to become a global leader in optimized therapies for certain gastrointestinal diseases. The company's proprietary clinical development pipeline specifically addresses innovative treatments for IBD, such as ulcerative colitis and Crohn's disease, and colon infections. Cosmo's most advanced development product is LIALDA™/ MEZAVANT™, a treatment for ulcerative colitis that is licensed globally to Giuliani and Shire Pharmaceuticals. Cosmo's proprietary MMX Technology is at the core of the company's product pipeline and was developed from its expertise in formulating and manufacturing gastrointestinal drugs for international clients at its GMP (Good Manufacturing Practice) facilities in Lainate, Italy. For further information on Cosmo, please visit the Company's website: www.cosmopharmaceuticals.com.

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

Statements included herein that are not historical facts are forward-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'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's Attention Deficit and Hyperactivity Disorder ("ADHD") franchise; patents, including but not limited to, legal challenges relating to Shire's ADHD franchise; government regulation and approval, including but not limited to the expected product approval date of INTUNIVTM (guanfacine) extended release (ADHD); Shire's ability to secure new products for commercialization and/or development; Shire's ability to benefit from its acquisition of New River Pharmaceuticals, Inc.; the successful development of JUVISTA® (human TGFâ3) and other risks and uncertainties detailed from time to time in Shire plc's filings with the Securities and Exchange Commission, particularly Shire plc's Annual Report on Form 10-K for the year ended December 31, 2006.

LIALDA™ is a trademark of Shire LLC.

MMX® is a registered trademark owned by Cosmo Technologies Ltd, Ireland, a wholly-owned subsidiary of Cosmo Pharmaceuticals SpA.


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