Washington Editor

Centocor Inc. on Monday added another indication to the lengthening list of uses of the monoclonal antibody Remicade.

This time around, the FDA cleared Remicade (infliximab) for long-term remission-level control of symptoms associated with Crohn's disease. The product already was approved to reduce signs and symptoms in moderately to severely active Crohn's in patients who have had an inadequate response to conventional therapy.

The long-term indication was based on a 54-week trial (called ACCENT I) of 545 patients in North America, Europe and Israel with moderate to severe disease. The endpoints were the proportion of patients who responded at week two and were still in remission at week 30, and the time to loss of response through week 54 in patients who responded.

Under the new indication, doses will be administered three times in the first six weeks, and every eight weeks thereafter. The original short-term indication entailed only one infusion.

Remicade targets and irreversibly binds to TNF-alpha. Overproduction of TNF-alpha is believed to play a role in Crohn's and rheumatoid arthritis (RA) and may also be important in a range of other immune-mediated inflammatory disorders, according to a statement released by Centocor, a Johnson & Johnson company based in Malvern, Pa.

Indeed, Remicade also is approved for reducing the number of draining enterocutaneous fistulas in patients with fistulizing Crohn's disease. The FDA is expected to release a decision early next year on a supplemental application for long-term control of the drug in that indication.

"For the first time, we have a therapy that can both induce and maintain remission-level control of disease symptoms, in many cases, while reducing or eliminating the need for steroid use," Gary Lichtenstein, an associate professor of medicine, director of the Center for Inflammatory Bowel Diseases, Hospital of the University of Pennsylvania, said in a prepared statement. "This is a significant advance."

Remicade, which generated about $700 million worldwide in 2001 sales, also is approved in three RA indications.

In early March, the FDA cleared the use of Remicade with methotrexate to help improve physical function in patients suffering from moderately to severely active RA who do not respond to methotrexate alone. Prior to that, it was approved in combination with methotrexate as a treatment for the reduction of signs and symptoms of RA and for inhibiting the progression of joint damage. (See BioWorld Today, March 1, 2002; July 13, 2000; and Nov. 11, 1999.)

Crohn's is a gastrointestinal disorder that affects more than half a million Americans. It causes inflammation of the gastrointestinal tract, typically resulting in symptoms such as diarrhea, fever, abdominal pain and weight loss.

Remicade also is the subject of studies in psoriasis, ulcerative colitis and spondyloarthropathies (such as ankylosing spondylitis and psoriatic arthritis).

Centocor has rights to Remicade in the U.S., and Schering-Plough Corp. has rights outside the U.S., except in Japan and parts of the Far East, where Osaka, Japan-based Tanabe Seiyaku Ltd. has rights.