Basingstoke, UK and Philadelphia, US June 17, 2008 Shire Limited (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced the publication of data from a randomized, long-term safety and tolerability study (study 303) of ulcerative colitis (UC) drug Lialda™ (mesalamine). The primary endpoints of this study were to assess the safety and tolerability of Lialda in mild-to-moderate UC patients over 12 months. Data were published in the July issue of Gut, the official journal of the British Society of Gastroenterology, a leading international journal in gastroenterology.
"This published data demonstrates that Lialda is generally well tolerated and has a strong safety profile," said Gary R. Lichtenstein, MD, co-author of study 303 and director of the Center for Inflammatory Bowel Diseases at the Hospital of the University of Pennsylvania. "Not only does this data demonstrate Lialda's safety and tolerability, but secondary endpoints from the maintenance phase of the 303 study show that a majority of patients on Lialda continued to remain in remission through 12 months."
Specifically, the primary endpoints of the Phase III, open-label, 12-month extension study were to evaluate the safety and tolerability of Lialda dosed once (2.4g/day) or twice daily (1.2g twice daily) over 12 months, including adverse events (AEs), treatment exposure, and time to withdrawal. AEs refer to any untoward medical occurrence that happens in a clinical trial patient. AEs can be "treatment-related" (TRAEs) and occur as a result of the study drug or they can be considered unrelated to the study drug. In study 303, all AEs were classified in one of three categories according to severity: mild, moderate, or severe.
Results of the study showed Lialda demonstrated a good safety profile, with 37.9 percent of patients (safety population n=459) experiencing AEs, the majority of which were mild or moderate in intensity. Treatment-related AEs were experienced by a total of 10.2 percent of patients [11.1 percent of patients (n=225) in the once-daily group and 9.4 percent of patients (n=234) in the twice-daily group]. A total of 3.9 percent of patients experienced serious AEs [4 percent of patients (n=225) in the once-daily group and 3.8 percent of patients (n=234) in the twice-daily group], most of which were gastrointestinal disorders, and only one serious AE was considered to be related to study treatment.
The secondary endpoints of the study evaluated maintenance of remission and relapse rates over 12 months. In the efficacy population at entry (month 0), 78.1 percent of patients (n=219) in the once-daily group and 82.3 percent of patients (n=232) in the twice-daily group were in clinical and endoscopic remission. At month 12, 64.4 percent of patients in the once-daily and 68.5 percent of patients in the twice-daily group were in strictly defined clinical and endoscopic remission (P=0.351). Thus, there was no significant difference between the once-daily and twice-daily groups with respect to strictly defined clinical and endoscopic remission at month 12. Further, 88.9 percent and 93.2 percent of patients in each group, respectively, had maintained clinical remission and were considered "relapse-free".
A total of 459 patients were enrolled and randomized in the 303 long-term safety study (246 directly from the 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 213 patients who received an additional 8 weeks of treatment with Lialda 4.8 g/day to induce remission). Remission was defined using stringent clinical and endoscopic measures: modified UC Disease Activity Index (UC-DAI) score of ≤1, with scores of 0 for rectal bleeding and stool frequency, and 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.