HONOLULU, Nov. 1 /PRNewswire/ - Results of two Phase III clinical studies (301 and 302) of an advanced formulation of high-strength mesalamine, SPD476, were presented today at the ACG in Honolulu, Hawaii. These results demonstrated that SPD476 met its primary endpoint of induction of remission of active, mild-to-moderate UC and was well tolerated as once-daily and twice- daily dosing.
Although mesalamine is routinely used for the treatment of UC, SPD476 utilizes an advanced proprietary Multi-Matrix System(TM) (MMX) technology to provide the highest mesalamine dose per tablet (1.2g) and deliver delayed and extended medication consistently through the colon.
Study 302 was a double-blind, multi-center Phase III study that studied the efficacy and tolerability of SPD476 compared to placebo. Asacol was included in the study as a reference arm. Three hundred and forty three subjects with active, mild-to-moderate UC were randomized to receive placebo, Asacol 2.4g/day (given three times daily), SPD476 2.4g (given once daily/QD) or SPD476 4.8g (given once daily) for eight weeks.
A statistically significantly greater population of patients receiving SPD476 2.4g (once daily) or 4.8g (QD) achieved remission compared to placebo (primary endpoint). Remission rates were 41.2%, 40.5%, 32.6% and 22.1% for SPD476 4.8g (QD), SPD476 2.4g/day (QD), Asacol and placebo, respectively. Similarly, SPD476 2.4g/day and 4.8g/day (QD) significantly increased clinical remission (complete resolution of symptoms) compared with placebo. Asacol was not statistically superior to placebo for either endpoint. A higher proportion of patients receiving active treatment achieved significant clinical improvement versus placebo.
"This study shows that once-daily SPD476 achieved the rigorous endpoint of induction of remission and was well tolerated for the treatment of UC," said Dr. William Sandborn, a key author of the 302 study. "These findings are very important to advancing UC therapy."
A second pivotal Phase III study, Study 301, was a multi-center, prospective, double-blind study designed to evaluate the safety and efficacy of SPD476 given once daily or twice daily versus placebo in adult patients with acute, mild-to-moderate UC. Two hundred and eighty patients were randomized to receive a placebo, SPD476 2.4g/day (given 1.2g BID) or SPD476 4.8g/day (given QD) for eight weeks.
The percentage of patients achieving remission was statistically significantly higher for SPD476 2.4g/day (BID) and 4.8g/day (QD) compared to placebo. Remission rates were 29.2%, 34.1% and 12.9% for SPD476 4.8g (QD), 2.4g/day (BID) and placebo, respectively. In addition, both SPD476 dosing regimens also provided for statistically significantly superior clinical improvement, clinical remission and sigmoidoscopic improvement from baseline compared with placebo.
"Because of the convenience of a once-daily dosing, SPD476 has the potential to improve patient compliance," said Study 301 lead investigator Dr. Gary Lichtenstein. "It also offers consistent delivery of mesalamine through the colon, thanks to the MMX delivery system, which may positively affect overall treatment success."
Previous studies of UC patients have demonstrated that up to 68% of patients do not regularly take the medication needed to control their condition, despite orders from their doctors.(1)
"Many patients find it difficult to take medication multiple times each day, even if it manages symptoms and improves life quality," said Rodger DeRose, CEO of the Crohn's and Colitis Foundation of America (CCFA). "A therapeutic option that makes this easier and proves effective is good news for patients who suffer from UC."
Shire is continuing the development of SPD476.
Shire has licensed from Giuliani S.p.A. the exclusive right to develop and commercialize SPD476 in the US, Canada and Europe (excluding Italy). Giuliani S.p.A. retains the development and commercialization rights to SPD476 in Italy.
About Mesavance (SPD476)
SPD476 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 ulcerative colitis. The most common adverse events reported in SPD476 Phase III studies were headaches (4.5%) and flatulence (3.4%).
Shire Pharmaceuticals Group plc
Shire Pharmaceuticals Group plc (Shire) is a global specialty pharmaceutical company with a strategic focus on meeting the needs of the specialist physician and currently focuses on developing projects and marketing products in the areas of central nervous system (CNS), gastrointestinal (GI), renal diseases and human genetic therapies. Shire has operations in the world's key pharmaceutical markets (US, Canada, UK, France, Italy, Spain and Germany) as well as a specialist drug delivery unit in the US.
For further information on Shire, please visit the Company's website: www.shire.com.
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 MTS (METHYPATCH) (ADHD), SPD503 (ADHD), SPD465 (ADHD), SPD476 (ulcerative colitis), I2S (iduronate-2-sulfatase) (Hunter syndrome), and NRP104 (ADHD), including its scheduling classification by the Drug Enforcement Agency in the United States; Shire's ability to benefit from its acquisition of Transkaryotic Therapies Inc.; Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year to December 31, 2004.
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. It 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 CCFA
The Crohn's & Colitis Foundation of America's (CCFA) mission is to cure and prevent Crohn's disease and ulcerative colitis through research, and to improve the quality of life of children and adults affected by these digestive diseases through education and support. More than 80 cents of every dollar the Foundation spends goes to mission-critical programs. CCFA consistently meets the standards of organizations that monitor charities, including the Better Business Bureau's Wise Giving Alliance (give.org) and the American Institute of Philanthropy (charitywatch.org). For more information, contact CCFA at 800-932-2423 or visit www.ccfa.org.
(1) Kane, S. Adherence issues in the patient with inflammatory bowel disease. Practical Gastroenterology. September 2004; 28(9): 16-22. Contacts: Elizabeth Schupp Baxter May Baccari Euro RSCG Life PR Euro RSCG Life PR Office: 212-845-4212 On-site: 253-230-3789 Email: elizabeth.baxter@eurorscg.com Email: may.baccari@eurorscg.com
Shire Pharmaceuticals Group plcCONTACT: Elizabeth Schupp Baxter, +1-212-845-4212,elizabeth.baxter@eurorscg.com, or May Baccari, On-site, +1-253-230-3789,may.baccari@eurorscg.com, both of Euro RSCG Life PR
