Philadelphia, PA October 15, 2007 Post-hoc and other analyses of secondary endpoints of a long-term safety and tolerability study of Shire plc's (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) ulcerative colitis (UC) drug LIALDA (mesalamine) provide further data on LIALDA in patients with mild to moderate ulcerative colitis. These analyses of LIALDAs 303 trial, a long-term, Phase III, open-label 12-14 month extension study, are being presented this week at The American College of Gastroenterology (ACG) meeting in Philadelphia.
The primary endpoint of study 303 was safety and tolerability and findings that LIALDA is generally well tolerated in mild to moderate UC patients were presented at the British Society of Gastroenterology (BSG) meeting in Glasgow, Scotland in March 2007.
"Earlier studies showed that LIALDA is well-tolerated and effective at inducing remission in patients with active, mild to moderate UC. Post-hoc analysis of secondary endpoints provided evidence that LIALDA maintained remission in a variety of UC patients, said Gary R. Lichtenstein, M.D., director of the Center for Inflammatory Bowel Diseases at the Hospital of the University of Pennsylvania.
A summary of key scientific presentations of post-hoc analyses of secondary endpoints of study 303 follows.
Once or Twice Daily LIALDA for Mild vs. Moderate Ulcerative Colitis Poster Presentation: Tuesday, October 16, 2007, Exhibit Hall B, #950
A post-hoc analysis of secondary endpoints from the long-term 303 study was performed to review the efficacy of LIALDA for maintaining remission in patients with mild versus moderate ulcerative colitis. In the 303 study, patients were randomized to receive LIALDA 2.4g/day (given once daily [QD]) or 2.4g/day (1.2g given twice daily [BID]). Study 303 defined patient remission 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, 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. Of the 451 patients included in the analysis, this post-hoc analysis showed that 70.5 percent (117/166) of patients with mild ulcerative colitis and 64.2 percent (183/285) of patients with moderate ulcerative colitis were in remission at 12 months.
LIALDA for Maintenance of Remission of Mild-to-Moderate Ulcerative Colitis Irrespective of Patient's Previous Relapse History Poster Presentation: Sunday, October 14, 2007, Exhibit Hall B, #283
A different post-hoc analysis of secondary endpoints from study 303 was done to understand the effect of relapse history in patients with mild-to-moderate ulcerative colitis on the efficacy of maintenance therapy. A total of 438 patients with complete relapse records at baseline (prior to enrolling in either parent study 301 or 302) were analyzed in this post-hoc analysis with LIALDA 2.4g/day. Of patients who previously experienced <3 relapses in the two years prior to parent study baseline, the analysis showed 70.1 percent (192/274) achieved remission at 12 months. In comparison, 59.8 percent (98/164) of patients who previously experienced ≥3 relapses in the two years prior to parent study baseline achieved remission at 12 months.
LIALDA for Maintenance in Both Left-Sided and Extensive Ulcerative Colitis Poster Presentation: Tuesday, October 16, 2007, Exhibit Hall B, #949
Another post-hoc analysis of secondary endpoints from study 303 assessed the efficacy of LIALDA 2.4g/day (given once daily or in two divided doses) for the maintenance of remission in ulcerative colitis patients with a medical history of either a left-sided or extensive condition. Of the 450 patients with known extent of disease included in the analysis, it was demonstrated that 67 percent (233/348) and 64.7 percent (66/102) of the patients with left-sided or extensive disease, respectively, were in remission at 12 months.
Post-hoc analysis of secondary endpoints of pivotal trials shows LIALDA offers initial resolution of UC symptoms within weeks
Also being presented at ACG are secondary endpoints from LIALDAs pivotal trials, the 301 and 302 studies, which were eight-week, phase III, placebo-controlled, double-blind, double-dummy studies.
Time to Initial Symptom Resolution with LIALDA for Active, Mild to Moderate Ulcerative Colitis Poster Presentation: Monday, October 15, 2007, Exhibit Hall B, #619
An important endpoint for both patients and physicians when treating active, mild-to-moderate ulcerative colitis is the time between initiation of therapy and initial symptom resolution. A post-hoc analysis of pooled data from the LIALDA 301 and 302 studies examined the treatment time required for patients to experience initial symptom resolution of rectal bleeding and normalization of stool frequency. Patients with active, mild-to-moderate UC were randomized to receive LIALDA 2.4g/day (given once or twice daily) or 4.8g/day (given once daily) or placebo, for eight weeks. The time required for patients to reach an initial resolution of symptoms was analyzed and defined as the time between the first dose of medication and the first day of symptom resolution. A total of 517 patients were included. This post-hoc analysis showed median time to initial resolution of symptoms (stool frequency and rectal bleeding) was 25, 26 and 44 days, in the LIALDA 2.4g/day (n=172), 4.8g/day (n=174) and placebo (n=171) groups, respectively. The data in this post-hoc analysis included both stool frequency and rectal bleeding when determining the median time to initial resolution of symptoms.
Other posters to be presented at ACG include: