Specialty biopharmaceutical company Shire has announced the results from the Phase 3 PREVENT2 trial of its once-daily SPD476, MMX mesalamine in ulcerative colitis patients with a history of diverticulitis.
The PREVENT investigational programme consists of PREVENT1 and PREVENT2 trials, which are randomised double-blind dose-response stratified placebo-controlled studies of SPD476 with an identical design.
The PREVENT2 study randomised 592 subjects to receive once-daily SPD476, MMX mesalamine 1.2g, 2.4g or 4.8g, or placebo for 104 weeks, to evaluate the safety and efficacy of SPD476 versus placebo in reducing the incidence of recurrent attacks of diverticulitis in patients with a history of at least one prior attack.
Recurrence of diverticulitis was defined as the presence of abdominal pain, a 15% increase in white blood cell count from baseline, and bowel wall thickening and / or fat stranding as evidenced by a spiral computerised axial tomography scan.
In the study, SPD476 failed to meet the primary endpoint in reducing the rate of recurrence of diverticulitis over a two-year treatment period, and also did not show a difference compared to placebo on the key secondary endpoint of the study.
Shire Specialty Pharmaceuticals and Regenerative Medicine businesses Research and Development senior vice president Jeffrey Jonas said PREVENT2 is a large, well-controlled trial, provided the company with important information regarding diverticulitis.
"We will continue to analyse these data and those of the second study, PREVENT1, which was similar in design to PREVENT2 and will report later in the year. Although the results of the second trial are pending, it is our current intention not to pursue a regulatory filing for this indication for MMX mesalamine," Jonas added.
SPD476, MMX mesalamine is an anti-inflammatory drug, with each delayed-release tablet containing 1.2g of 5-aminosalicylic acid (5-ASA, mesalamine).
In the US, SPD476 has been registered as Lialda and is approved for the induction of remission in patients with active, mild to moderate ulcerative colitis and for the maintenance of remission of ulcerative colitis.
SPD476 is registered as Mezavant/Mezavant XL in Europe for the induction of clinical and endoscopic remission in patients with mild to moderate, active ulcerative colitis and for maintenance of remission.