Washington, D.C. - May 22, 2007 - A long-term phase III, open-label 12-14 month extension study (303) presented at the British Society of Gastroenterology (BSG) meeting in Glasgow, Scotland in March 2007 showed Shire plc's (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) LIALDA™ (mesalamine) is well tolerated in mild to moderate UC patients. Today, secondary endpoints of study 303 were presented as post-hoc analyses at Digestive Disease Week (DDW).
Approved by the FDA on January 16, 2007, for the induction of remission in patients with active, mild to moderate UC, LIALDA is the first and only oral once-daily mesalamine on the market. Safety and effectiveness have been established for up to eight weeks. LIALDA is being evaluated for longer term use.
Long-term remission and relapse rates on LIALDA (abstract # T1296)
A post-hoc analysis of study 303 evaluated maintenance of remission and relapse rates over 12 months. Remission was defined using stringent clinical and endoscopic criteria: modified UC Disease Activity Index (UC-DAI) score of ≤1, with scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment and sigmoidoscopy score of ≤1, with a sigmoidoscopy score reduction of ≥1 point from baseline and no mucosal friability. Relapse was defined as withdrawing from the study due to a need for alternative therapy for UC.
Overall, a total of 459 patients entered the maintenance phase of study 303. Of these patients, 362 patients met the stringent remission criteria (clinical and endoscopic as defined above) at baseline (in parent studies 301 and 302 - LIALDA's eight-week, phase III, placebo-controlled trials that demonstrated efficacy for the induction of remission in active, mild to moderate UC) and received LIALDA once daily (2.4g/day; n=171) or twice daily (2.4g/day; n=191) for 12 months as part of study 303.
The analysis found that 67.8 percent of the 171 patients on once-daily LIALDA remained in remission and 88.7 percent of these patients remained relapse free at the end of 12 months.
"Earlier studies showed that LIALDA is effective at inducing remission in patients with active, mild to moderate UC. We were encouraged when we did this secondary analysis and found that more than two-thirds of patients in the maintenance phase of study 303 remained in remission and nearly 90 percent of patients did not relapse," says Asher Kornbluth, M.D., Associate Clinical Professor of Medicine at The Mount Sinai Medical Center.
Long-term remission rates regardless of 5-ASA treatment (abstract # T1295)
Another post-hoc analysis of the 303 extension study investigated those patients on a 5-ASA who achieved remission or were deemed to be sufficiently controlled by the physician in study 301 (patients received LIALDA) and study 302 [patients received LIALDA or Asacol® (mesalamine)] to determine if they had remained in remission when staying on or changing to LIALDA for 12 months.
A total of 198 patients who received LIALDA or Asacol in the parent studies entered the maintenance phase of study 303 directly. Of these patients, 151 were in clinical and endoscopic remission, while 47 were considered well enough by their physician to receive maintenance treatment.
Study findings show approximately 75 percent (n=148/198) of patients remained in remission on LIALDA after 12 months, regardless of whether they were previously on LIALDA or Asacol: 73.4 percent (58/79) for patients previously on LIALDA once or twice daily (2.4g/day); 74.7 percent (62/83) for patients previously on LIALDA once daily (4.8g/day); and 77.8 percent (28/36) for patients previously on Asacol three times daily (2.4g/day).
Cumulative analysis across three studies with LIALDA as sole therapy (abstract # T1297)
Another post-hoc analysis assessed long-term remission and relapse rates (secondary endpoints) of study 303. The analysis evaluated data from patients taking Lialda from all three studies: 301, 302, and 303. Patients in the parent studies (301 and 302) who did not achieve remission after eight weeks on Lialda were eligible for enrollment in the acute phase of study 303. In this acute phase, they were given a higher dose of Lialda (4.8g/day, once daily) for an additional eight weeks to induce remission. In total, 63.6 percent of patients (n=220/346) treated with Lialda for up to 16 weeks achieved remission.
Those patients, who achieved remission either in the parent studies (n=125), or the acute phase of study 303 (n=95), were allowed to enter the 12-month maintenance phase of study 303. Of the 220 patients who were in remission, 218 patients actually entered the maintenance phase.
A combined analysis of both long-term remission rates and relapse rates showed that of the patients who started on Lialda therapy, 56.6 percent achieved remission and remained relapse free for at least one year.
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 UC. LIALDA is indicated for the induction of remission in patients with active, mild to moderate UC. 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. LIALDA is the only ulcerative colitis treatment that utilizes MMX™ Technology. LIALDA with MMX Technology combines a pH dependent gastro-resistant coating, which delays the release of the medication to the colon (the site of the inflammation in ulcerative colitis), with a tablet core containing mesalamine with hydrophilic and lipophilic excipients.
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.
UC is a type of inflammatory bowel disease that produces inflammation and sores or ulcers along the inside of the large intestine, also called the bowel or colon. The sores may interfere with the normal digestive process, often causing cramping, bloating, diarrhea, bleeding, fatigue, weight loss and frequent bowel movements. This serious, chronic autoimmune disease affects approximately 700,000 Americans. For more information on UC, visit www.managinguc.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'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 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. 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.
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, 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.
Digestive Disease Week
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 (AGA) Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 19-24, 2007, at the Washington Convention Center, Washington, DC. 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 www.ddw.org.
THE "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 dates of SPD503 (guanfacine extended release) (ADHD) and SPD465 (extended release triple-bead mixed amphetamine salts) (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.; 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 trademark owned by Cosmo Technologies Ltd, Ireland, a wholly-owned subsidiary of Cosmo Pharmaceuticals SpA.
Asacol® is a registered trademark of Procter & Gamble Pharmaceuticals.