PHILADELPHIA – October 6, 2008 – Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, announced the results from a multidisciplinary analysis of in vitro and in vivo data of LIALDA® (mesalamine) versus Asacol® (mesalamine) that investigated factors including transit and disintegration of tablets along with tablet coating thickness that may affect a consistent release of 5-aminosalicylate acid (5-ASA) in both therapies. This analysis will be presented at The American College of Gastroenterology (ACG) meeting in Orlando.

"Previous studies have demonstrated that LIALDA is an effective and generally well-tolerated treatment for patients who have active, mild-to-moderate UC," said Srini Tenjarla, PhD, lead study investigator and senior director of pharmaceutical sciences at Shire. "The time of initial release of 5-ASA in the colon, as well as the duration of continued release, is important in the treatment of UC. Now, through a combination of analyses, we have data that shows LIALDA demonstrated a steady 5-ASA release throughout the entire colon."

The clinical significance of the results from this analysis has not been established. This analysis was not designed to evaluate or compare the clinical efficacy of LIALDA and Asacol.

Understanding 5-Aminosalicyclic Acid Release Profiles from pH-dependent, Delayed-release Formulations: A Multidisciplinary Approach Poster Presentation: Tuesday, October 7, 2008, Florida Exhibit Halls

Recent data from scintigraphic and imaging and dissolution studies, Study 1 and Study 2 respectively, of LIALDA and two formulations of Asacol (Giuliani SpA, Italy in Study 1 and P&G, Cincinnati OH as reported by Spencer et al in Study 2) was gathered to evaluate factors that affect the release of each 5-ASA formulation.

Study 1 was an open-label, single-dose, two-way cross-over study during which healthy subjects (n=8) were randomized to receive LIALDA or Asacol (Giuliani SpA, Italy). Subjects received either a single radiolabeled LIALDA tablet (one 1.2 g radiolabeled tablet) or three radiolabeled tablets of pH-dependent, delayed-release mesalamine (400 mg radiolabeled tablets) as a single dose, and crossed over to the other treatment after a washout period of ≥7 days. Scintigraphic images were taken to evaluate the transit and disintegration of the tablets, as well as the distribution of 5-ASA through the GI tract. Images were taken at 20-minute intervals until eight hours post-dose, at 30-minute intervals until 16 hours post-dose, and at two-hour intervals until 24 hours post-dose.

Results of Study 1 found that initial disintegration of LIALDA occurred in the GI tract between the mid-small bowel and ascending colon at 4.75±1.31 hours after dosing and initial disintegration of Asacol occurred between the distal small bowel and the transverse colon at 6.16±1.80 hours after dosing. [Initial disintegration was defined as the mean hours ± standard deviation (SD).] Further, complete disintegration occurred in the GI tract for LIALDA (between the ascending and descending colon 17.37±8.63 hours following dosing and complete disintegration of Asacol occurred between the iliocaecal junction and the transverse colon 7.27±2.13 hours following dosing, with the vast majority of disintegration occurring in the ascending colon. Overall, scintigraphic data suggest a steady release of 5-ASA from radiolabeled LIALDA, with a prolonged period of disintegration throughout the colon.

Study 2 (imaging and dissolution) utilized non-destructive, three-dimensional terahertz pulse imaging to measure mean coating thickness of LIALDA tablets from three batches. This study was conducted according to the methodology described by Spencer et al (J Pharm Sci, 2008). Dissolution testing was subsequently performed on the same tablets at pH 6.8 and 7.2 (to represent altered pH in the GI tract of patients with UC) using USP II apparatus (50 rpm).

Results of Study 2 showed that the coating thickness of LIALDA ranged from 109.2 µm (±16.8) to 113.8 µm (±19.8). Additionally, LIALDA tablets demonstrated steady release of 5-ASA at both pH values with complete release achieved over >8 hours at pH 6.8 and over >12 hours at pH 7.2.

Combined results of the two studies (Study 1 and Study 2) suggest that 5-ASA will be released from LIALDA in a consistent and steady manner throughout the colon.

Also being presented at ACG is a post hoc analysis of secondary endpoints from LIALDA Study 303, which evaluated the time to resolution of symptoms in UC patients taking up to eight additional weeks of high-dose LIALDA (4.8 g/day). The primary endpoints of Study 303, a long-term, open-label, phase III extension study, were safety and tolerability of LIALDA over 12 months.

MMX Mesalamine Therapy for the Induction of Remission Beyond Eight Weeks: How Long Before Symptom Resolution? Poster Presentation: Sunday, October 5, 2008, Florida Exhibit Halls

A post hoc analysis of secondary endpoints from the long-term 303 safety study was conducted to evaluate when patients (n=304) with active, mild-to-moderate UC who did not achieve clinical and endoscopic remission in two LIALDA Phase III studies (parent studies 302 and 301) after up to eight weeks could achieve complete symptom resolution when they received up to 16 weeks of treatment of LIALDA. Patients in the original 301 and 302 studies were randomized to receive placebo, LIALDA 2.4 g/day, LIALDA 4.8 g/day, or Asacol 2.4 g/day for eight weeks. All patients enrolled in the 303 extension study received LIALDA 4.8 g/day (given 2.4 g BID) for up to an additional eight weeks.

Clinical and endoscopic remission was stringently defined as a total modified UC Disease Activity Index (UC-DAI) score of ≤1, calculated as: scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment (PGA) score and sigmoidoscopy score of ≤1, with no mucosal friability, and a ≥1-point reduction from baseline in sigmoidoscopy score. Time to initial resolution of symptoms was estimated using Kaplan-Meier methodology. Time to initial symptom resolution was defined as the time between the first dose of study medication and the first day of rectal bleeding cessation and stool frequency normalization based on the modified UC-DAI.

In total, nearly 60 percent (59.5 percent) of patients (181/304) who continued treatment with LIALDA 4.8 g/day in the 303 extension study achieved clinical and endoscopic remission. The median time to initial resolution of UC symptoms (defined as the day when 50 percent of patients achieved symptom resolution) in patients who had achieved clinical and endoscopic remission with up to an additional eight weeks of LIALDA was 15 days.