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FDA Grants Tentative Approval to Budesonide (Uceris) Rectal Foam for Treatment of Distal Ulcerative Colitis
The FDA has given a tentative green light to budesonide (Uceris, Salix Pharmaceuticals) rectal foam for the induction of remission in patients with active mild-to-moderate distal ulcerative colitis (UC) extending up to 40 cm from the anal verge. The rectally administered corticosteroid is expected to be launched during the first quarter of 2015.
Two identically designed, randomized, double-blind, placebo-controlled, phase III studies were conducted to evaluate the efficacy and safety of budesonide rectal foam for the induction of remission in patients with mild-to-moderate distal UC.
A total of 546 patients with endoscopically confirmed distal UC extending 5 cm or more, but no further than 40 cm, from the anal verge, and with a baseline Modified Mayo Disease Activity Index (MMDAI) score between 5 and 10, inclusive, with subscale ratings of 2 or 3 for endoscopic appearance and rectal bleeding, were eligible for the studies. The patients were randomly assigned to receive budesonide rectal foam (2 mg/25 mL; n = 267) or placebo (n = 279) twice daily for 2 weeks, and then once daily for 4 weeks. Concomitant use of oral 5-aminosalicylic acid (5-ASA) drugs at doses of up to 4.8 g/d was permitted.
A significantly greater percentage of patients receiving budesonide 2 mg rectal foam achieved remission of distal UC at 6 weeks compared with placebo (41.2% vs. 24.0%, respectively). Significantly more patients treated with budesonide rectal foam also achieved key secondary outcome measures compared with placebo at 6 weeks, including Modified Mayo Disease Activity Index (MMDAI) endoscopy scores of 0 or 1 in 55.6% vs. 43.2%, respectively, in the first trial and in 56.0% vs. 36.7% in the second trial.
Moreover, a significantly greater percentage of patients treated with budesonide rectal foam experienced improvement in rectal bleeding within the first 2 weeks of treatment (twice- daily dosing); this percentage increased and was maintained after an additional 2 and 4 weeks of treatment once a day. At week 6, the percentage of patients achieving an MMDAI rectal bleeding score of 0 was 46.6% for budesonide vs. 28.0% for placebo in the first trial and 50.0% vs. 28.6% in the second trial.
The most common adverse events associated with budesonide rectal foam included decreased blood cortisol levels (17.2%), adrenal insufficiency (3.7%), nausea (2.2%), and headache (2.2%).
UC is a chronic disease in which the lining of the colon becomes inflamed and develops small ulcers, which produce pus and mucous. The combination of inflammation and ulceration can cause abdominal discomfort and frequent emptying of the colon. Distal UC is characterized as either ulcerative proctitis (inflammation localized to the rectum) or ulcerative proctosigmoiditis (inflammation localized to the distal colon and rectum).
The Crohn’s and Colitis Foundation of America (CCFA) estimates that UC affects approximately 700,000 Americans. While most people are diagnosed in their mid-30s, the disease can occur at any age, and affects men and women equally. An estimated 46% of people with UC have distal disease.
Rectal therapy is recommended for the induction of remission in patients with mild-to-moderate ulcerative proctitis, and is recommended alone or in combination with oral aminosalicyclic acid (ASA) for mild-to-moderate distal UC. However, currently available rectal therapies have limitations, including difficulty in administration and retention (enemas) and limited proximal spread (suppositories).
Source: Salix Pharmaceuticals; September 15, 2014.