Results of two clinical studies (202 and 301) of an advanced formulation of high-strength mesalazine, SPD476, were presented today at UEGW in Copenhagen, Denmark. Based on these Phase II and Phase III study results, SPD476 met its primary endpoint of induction of remission of mild-to-moderate UC and was well tolerated in a once-daily dosing.
Although mesalazine is routinely used for the treatment of UC, SPD476 utilizes an advanced Multi-Matrix System(TM) (MMX) technology to provide the highest mesalazine doses per tablet and deliver delayed and extended medication consistently throughout the colon.
Study 301 is a multi-center, prospective, double-blind, placebo-controlled Phase III 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.
"SPD476, via the MMX technology, may provide a significant advance in UC therapy," said Dr. Michael Kamm, one of the lead investigators of the Phase III study. "Once approved, SPD476 may improve patient compliance and overall treatment success."
In addition, Study 202, a Phase II, multi-center, double-blind, parallel-group, dose-ranging study, was presented. During the study, patients with mild-to-moderate UC received 1.2g, 2.4g or 4.8g of SPD476 once daily. An endpoint of induction of remission was used to evaluate patients. Remission was defined as complete resolution of symptoms combined with improved endoscopy score. A response to treatment was shown at doses of 2.4g/day and 4.8g/day.
"These results are important because they demonstrate the potential to induce remission with a once-daily therapy," said Dr. Geert D'Haens, one of the lead investigators in the Phase II study. "SPD476 may be a significant advance in 5-ASA therapy. Convenience is a key factor in helping patients lead normal and productive lives."
"UC is a chronic medical condition that can significantly reduce a person's quality of life, and we also know that patients have difficulty taking regular medication," said Rod Mitchell, Chairman of the European Federation of Crohn's & Ulcerative Colitis Associations (EFCCA). "Any treatment that shows efficacy and reduces the numbers of pills taken daily will be a welcome advance in UC therapy."
Shire is continuing the development of SPD476. Additional data on Phase III results of SPD476 will be presented in November at the annual meeting of the American College of Gastroenterology (ACG) in Honolulu.
Shire has licensed from Giuliani S.p.A the exclusive right to develop and commercialise SDP476 in the US and Europe (excluding Italy). Giuliani SDP476 retains the development and commercialisation rights to SPD476 in Italy.
SPD476 is a novel, high-dose 5-aminosalicylic acid (5-ASA; mesalazine) 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%).
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 disorders (hair loss).
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.
The European Federation of Crohn's & Ulcerative Colitis Associations was formally established in 1993 in Strasbourg, and its constitution was registered in Belgium in 1996. EFCCA is assisted by a Europe-wide team of eminent Medical Patrons. Over the past decade, EFCCA membership has risen to 22 European National IBD Patient Associations and it is estimated that there are a total of >1 million patients diagnosed with IBD in those countries.
EFCCA aims to improve the well being of patients of all ages with inflammatory bowel disease and their partners and families through working with and for the EFCCA Member National Associations and others throughout all of Europe; facilitating the exchange of information and the promotion of cross-frontier activities; effecting regular contact with the European authorities, doctors, health professionals and organisations and with others world-wide; and the encouragement of scientific research into crohn's and colitis (IBD) causes and treatment.
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