By Mary Welch
Less than six months after gaining FDA approval for Remicade (infliximab) to treat Crohn's disease, Centocor Inc. submitted a supplemental biologics license application (BLA) to market the monoclonal antibody for use against rheumatoid arthritis (RA).
Christopher Allman, spokesman for Malvern, Pa.-based Centocor, noted Remicade is the only treatment for Crohn's disease, but will compete with other drugs against RA.
"It depends on how the FDA reads the application, as to whether they grant it any special status," Allman said. "It's too early to predict."
Remicade is a human-mouse antibody that blocks the activity of tumor necrosis factor (TNF) alpha, a cytokine implicated as an over-stimulator of the immune system in several inflammatory disease, including Crohn's disease, RA and asthma. The drug is believed to reduce inflammation in rheumatoid arthritis patients by binding to and neutralizing TNF-alpha, a key inflammatory mediator, on the cell membrane and in the blood.
Centocor's application is based, in part, on results from a pivotal study called the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT), designed to evaluate the safety and efficacy of Remicade in combination with methotrexate in patients with active RA. The study was a 30-week, double-blind, placebo-controlled, randomized clinical trial of 428 patients at 34 sites in Europe and the U.S. It involved five trial arms, each including methotrexate, the standard immunosuppressant therapy. Most of the participants had been on methotrexate therapy for three or more years, with about half having progressive and advanced diseases.
"Methotrexate really is the gold standard for the treatment of RA," said Allman. "Physicians know it and use it as the first line of therapy. But if it doesn't work - and it doesn't work in a lot of cases - or it doesn't work to the level the patient wants, then what is your next step? We think it should be anti-TNF drug, used in combination [with methotrexate]."
Arms in the trial consisted of 3 milligrams per kilogram of body weight of Remicade every four weeks or every eight weeks; 10 mg of the drug in the same time periods; or placebo. Signs and symptoms of the disease were reduced 52 percent in the drug groups, as compared to 20 percent of the placebo group. (See BioWorld Today, Nov. 10, 1998, p. 1.)
The ATTRACT trial will last up to two years, as Centocor wants to evaluate the long-term use or Remicade in patients with RA.
Centocor's stock (NASDAQ:CNTO) closed Wednesday at $42.125, up $0.937. n