COPENHAGEN, Denmark -- 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 ulcerative colitis (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™ (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 percent, 34.1 percent and 12.9 percent 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 Michael Kamm, MD, 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 Geert D'Haens, MD, 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."
Previous studies of UC patients have demonstrated that up to 68 percent of patients do not regularly take the medication needed to control their condition, despite orders from their doctors.1
"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.
About SPD476
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 percent) and flatulence (3.4 percent).
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.
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 disorders (hair loss).
About EFCCA
The European Federation of Crohn's & Ulcerative Colitis Associations aims to improve the well being of patients of all ages with inflammatory bowel disease and their partners and families.
1. Kane, S. Adherence issues in the patient with inflammatory bowel
disease. Practical Gastroenterology. September 2004; 28(9): 16-22.
Source: Shire Pharmaceuticals Group plc