Time to initial resolution of rectal bleeding and high stool frequency in patients who achieved clinical and endoscopic remission after up to 8 weeks

STUDY 303: Long-term Safety Data on Mesalamine for Patients with Ulcerative Colitis

Objectives  Study design  Patient disposition  Definitions  Safety of 8-week acute extension  Efficacy of 8-week acute extension  Summary

Mesalamine 2.4 and 4.8 g/day Is Effective for the Induction of Remission  Lichtenstein et al. 1 and Kamm et al. 2 studies: Two double-blind, placebo-controlled, phase III studies evaluating the efficacy and tolerability of mesalamine  Both studies demonstrated mesalamine 2.4 g/day (given q.d. or 1.2 g b.i.d.) and 4.8 g/day (given q.d.) to be efficacious and well tolerated for the induction of remission in patients with active, mild-to-moderate ulcerative colitis Adapted from: 1 Lichtenstein et al. Clin Gastroenterol Hepatol 2007;5:95– Kamm et al. Gastroenterology 2007;132:66–75.

Mild (Score = 1) Moderate (Score = 2) Severe (Score = 3) Rectal bleeding  Streaks of blood  Obvious blood  Mostly blood Stool frequency  1-2/day > normal  3-4/day > normal  > 4/day > normal Mucosal appearance  Erythema  Decreased vascular pattern  Minimal granularity  Friability *  Marked erythema  Friability *  Granularity  Absent vascular pattern  Bleeding minimal trauma  No ulcerations  Ulceration  Spontaneous bleeding PGA (Physician’s Global Assessment)  Mild  Moderate  Severe * Friability moved from Score of 1 to 2 Adapted from Kamm et al. Gastroenterology 2007;132:66–75. Modified* UC-Disease Activity Index

End Point Definitions  Relapse: Withdrawal from the study due to a requirement for alternative treatment (including a dose increase or surgery) for an exacerbation of UC  Remission: Modified UC-DAI score  1, calculated as a score of 0 for rectal bleeding and for stool frequency, a combined Physician’s Global Assessment (PGA) and sigmoidoscopy score of  1, no mucosal friability, and a sigmoidoscopy score reduction of 1 point or more from baseline Adapted from Kamm et al. 2008;57(7):

STUDY 303 Efficacy Results: 8-Week Acute Extension Phase

(n = 107) (n = 78) (n = 41) Prior treatment Up to 8 weeks’ active treatment Up to 16 weeks’ active treatment

Number of patients (%) Adapted from Lichtenstein et al. Poster presented at ACG *Week 0=First study visit of the acute extension phase 8-Week Acute Extension Phase: Sigmoidoscopy Scores

STUDY 303 Acute Extension Phase Conclusions 1,2  Mesalamine 4.8 g/day (2.4 g dosed b.i.d.) was well- tolerated in the 8-week acute extension phase Safety profile similar to that of the parent studies (Lichtenstein et al. and Kamm et al.)  Mesalamine 4.8 g/day for up to 4 months was well- tolerated  Approximately 60% of patients achieved remission, using stringent clinical and endoscopic criteria Adapted from: 1 Lichtenstein et al. Poster presented at APhA Lichtenstein et al. Poster presented at ACG 2007.