By Lisa Seachrist

Washington Editor

WASHINGTON — Results from two Phase III studies of Centocor Inc.'s humanized monoclonal antibody against tumor necrosis factor (TNF), cA2, show the drug maintains remission in Crohn's disease patients as well as helps heal painful fistulae in two-thirds of these patients.

The two placebo-controlled studies of cA2 confirm results of Phase II trials presented last year and will serve as the basis of marketing approval applications in Europe and the U.S. at the end of this year.

Centocor's stock (NASDAQ:CNTO) gained $1.656 Monday, closing at $33.156.

"We are very excited by the data — there are essentially no approved therapies for this condition," said Thomas F. Schaible, director of Immunology and Clinical Research for the Malvern, Penn., company. "We know how cA2 is impacting their lives, that is what motivates us to try to get this drug registered as early as possible."

Crohn's disease is a chronic disorder characterized by inflammation of the gastrointestinal tract which leads to thickening of the bowel wall. The disorder affects approximately 1 million people in the U.S. and Europe and symptoms include diarrhea, fever, abdominal pain and weight loss. Standard treatments for the disease rely primarily on steroids

CA2 blocks the cytokine tumor necrosis factor which has been implicated as an overstimulator of the immune system in several inflammatory disorders including Crohn's disease.

The two studies presented Monday at the Digestive Disease Week, a meeting sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, were conducted in 18 centers in North America and Europe.

The first study was an extension of a trial presented last year which included 108 patients and showed that a single infusion of cA2 produced clinical improvement in two-thirds of patients as measured by a scale called the Crohn's Disease Activity Index (CDAI). By comparison, only 17 percent of the placebo treated group showed improvement. Thirty-three percent had remissions of their active Crohn's Disease.

In its extended form, seventy-three patients who showed clinical response to cA2 eight weeks after the initial infusion were re-randomized at week 12 for four more treatments given eight weeks apart of either cA2 or placebo. Sixty percent of the patients who received cA2 remained in remission for the duration of the treatment while patients on placebo saw their symptoms gradually worsen over time although 19 percent of the placebo patients were still in remission 48 week after their first infusion.

"Our follow up has shown that cA2 is well tolerated," said Stephan R. Targan, director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles. Targan participated in the study and presented the results. He added, "The duration of the clinical effect was welcome news."

Effect On Fistulae Called 'Dramatic'

The second study tested whether cA2 could have any effect on one of the major complications of Crohn's disease, fistulae -- extensions between the bowel and the skin which allow mucous and fecal material to drain out forming abscesses that can break through the skin. Fistulae can be quite painful and disfiguring.

Ninety-four patients with fistulae who had failed treatments with steroids were give three infusions of either cA2 or placebo. Two-thirds of the patients receiving cA2 had 50 percent of their fistulae close.

"The effect was quite dramatic," said Daniel H. Present, clinical professor of medicine at the Mount Sinai School of Medicine in New York. "If this proves to be safe in the long term, it will become a first line medication for the treatment of fistulae and Crohn's disease."

Centocor plans to start a trial later this summer in 300 patients to determine the optimal dose and duration of therapy in Crohn's patients. That study will examine treatment over the course of a year and look to see if patients taking cA2 can lower their doses of steroids as well as look for evidence that cA2 promotes mucosal healing in the intestine.

In addition, the company is developing the drug for use in rheumatoid arthritis (RA) and is presently conducting a Phase III trial of cA2 as a treatment for that disease.

"In Crohn's disease, there is a dire need for a new treatment," Schaible said. "CA2 may also provide a good alternative to drugs like methotrexate for RA." *