NORWICH EATON’s ASACOL (MESALAMINE) APPROVED

NORWICH EATON's ASACOL (MESALAMINE) APPROVED for treatment of mildly to moderately active ulcerative colitis on Jan. 31. The agency approved the NDA (19-651) for Asacol 400 mg delayed-release tablets following a review period of five years and four months. The anti-inflammatory was granted approvable status on Oct. 10, 1991. Under a five-year compassionate use program, Asacol has been given free of charge to 3,000 patients with ulcerative colitis who could not be treated with alternative therapies. Procter & Gamble subsidiary Norwich Eaton said that it will continue to provide Asacol on a compassionate use basis until the product is launched. The drug could be available in several weeks. FDA gave Asacol a "3P" designation, which means the drug is a new formulation of an already marketed compound that received a "priority" review from the agency. Solvay (formerly Reid-Rowell) markets Rowasa, a rectal suspension enema that contains 4 grams of mesalamine and suppositories with 500 mg of mesalamine. Rowasa enema was approved in December 1987 for the treatment of active mild to moderate distal ulcerative colitis, proctosigmoiditis or proctitis. Rowasa was the first mesalamine, or 5-aminosalicylic acid, product to be cleared by FDA. Asacol's labeling says that "mesalamine is thought to be the major therapeutically active part of the sulfasalazine molecule in the treatment of ulcerative colitis [and] sulfasalazine is converted to equimolar amounts of sulfapyridine and mesalamine by bacterial action in the colon." A number of sulfasalazine products are already marketed, including Kabi Pharmacia's Azulfidine oral suspension and delayed-release tablets. Asacol's delayed-release tabs are "coated with acrylic-based resin, Eudragit S, which dissolves at pH 7 or greater, releasing mesalamine in the terminal ileum and beyond for topical anti- inflammatory action in the colon," labeling says. "Mesalamine from orally-administered Asacol tablets appears to be more extensively absorbed than the mesalamine released from sulfasalazine." The tabs are manufactured and coated by the German firm Rohm Pharma, a joint venture between Rohm and Norwich Eaton. According to labeling, Asacol apparently has the advantage over sulfasalazine of not affecting male fertility. Norwich Eaton said that sulfapyridine, which is a component of sulfasalazine, has been associated with male infertility. "The effect of Asacol (mesalamine) on sulfasalazine-induced impairment of male fertility was examined in an open-label study," the labeling says. "Nine patients (age 40 years) with chronic ulcerative colitis in clinical remission on sulfasalazine 2-3 g/day were crossed over to an equivalent Asacol dose (0.8-1.2 g/day) for 3 months," the labeling notes. "Improvement in sperm count (p 0.02) and morphology (p 0.02) occurred in all cases [and] improvement in sperm motility (p 0.001) occurred in 8 of the 9 patients." Rowasa's labeling says: "The oligospermia and infertility in men associated with sulfasalazine have not been reported with mesalamine." Asacol's NDA was reviewed by FDA's Gastrointestinal Drugs Advisory Committee in September 1987. The panel voted four-to- three against recommending approval of the drug for induction of remission and maintenance therapy of ulcerative colitis because it felt that only one of the company's studies demonstrated efficacy. The committee also voted against recommending Asacol for second- line treatment of ulcerative colitis in patients intolerant of sulfasalazine, an indication that was proposed by some of the committee members. Asacol is also being studied for treatment of inflammatory bowel syndrome associated with HIV.