By Lisa Seachrist
WASHINGTON — Heeding the advice of an advisory panel that met in May, the FDA approved Centocor Inc.'s Remicade (formerly Avakine), a monoclonal antibody for the treatment of the debilitating bowel disorder, Crohn's disease.
The agency granted Centocor a relatively wide label, approving Remicade for use in patients with moderate or severe Crohn's disease for whom conventional therapy is inadequate and in patients who have draining fistulae. The label also indicates that Remicade is for short-term use.
"We think this is going to be a great option for Crohn's patients," said Christopher Allman, manager of corporate relations for Malvern, Pa.-based Centocor.
Remicade won't immediately be available for use, Allman noted. Physicians and their patients will have to wait until late September or early October before the drug is shipped to distributors. Centocor will sell the drug to distributors and wholesalers for $450 per vial, and the average Crohn's disease patient will require three to four vials of Remicade per infusion.
Crohn's disease is an autoimmune disorder that causes inflammation of the mucosal lining in the gastrointestinal tract. It affects about 1 million people in the United States and Europe. Symptoms include diarrhea, fever, abdominal pain and weight loss. Crohn's strikes mostly women between the ages of 20 and 35.
As the disease progresses, the inflammation may lead to fistulae, which are deep ulcer tracts that burrow through the bowel wall into surrounding tissues and out the surface of the skin. The fistulae can become infected, bleed and require large portions of the small and large intestines to be surgically removed.
Current therapies to quell the inflammation include prednisone, methotrexate, and other anti-inflammatory medications. These therapies inadequately control the disease and cause serious side effects.
Remicade, or infliximab, is a human-mouse antibody that blocks the activity of tumor necrosis factor (TNF) alpha, a cytokine implicated as an overstimulator of the immune system in several inflammatory diseases including Crohn's, rheumatoid arthritis and asthma.
The FDA based its decision to approve the drug largely on two clinical trials of the drug in Crohn's patients. The first study looked at 108 patients with moderate to severe Crohn's disease who inadequately responded to conventional therapies. Eighty-two percent of patients who were treated with a single infusion at the approved dosage of 5 milligrams per kilogram of body weight achieved a clinical response four weeks following the infusion, compared with 16 percent of patients receiving placebo. In addition, 48 percent of patients treated with Remicade went into clinical remission by week four, compared with 4 percent of the control patients.
Label Mirrors Dosages Used In Clinical Trials
In the second study of 94 patients with fistulae, 68 percent of those treated with the approved dosage of Remicade — an initial dose of 5 milligrams per kilogram of body weight, followed by similar doses at week 2 and week 6 — had closure of at least 50 percent of fistulae for four weeks, compared to 26 percent of placebo patients.
"The label really reflects the studies that we have done," Allman said. "We will be continuing to look at the long-term effects of the drug in a repeat use study during the postmarket period."
Remicade has side effects which include nausea, upper respiratory infections and abdominal pain. In addition, some patients suffered from infusion reactions and infections. Remicade therapy may result in the development of autoantibodies.
The company is investigating Remicade's use in pediatric Crohn's and its ability to lessen patient dependence on steroids. Centocor plans to announce the results of a Phase III study of the drug in rheumatoid arthritis in November at the American College of Rheumatology meeting. The company also intends to start trials of the drug in patients with asthma next year.
Centocor has retained exclusive marketing rights for Remicade in the United States. Following regulatory approvals in their respective countries, Osaka-based Tanabe Seiyaku Co. Ltd. will market the product in Japan and the Far East, while Schering-Plough Corp., of Madison, N.J., will market Remicade in all other countries throughout the world.
"Remicade is the most important growth driver for Centocor," said Jay Silverman, an analyst with BancAmerica Robertson Stephens & Co, in San Francisco. "By my calculation every dollar of Remicade sales is 3 times more profitable than ReoPro."
Silverman said that the fact that Centocor retains all U.S. marketing rights to Remicade substantially increases the drug's value. The profit from the company's heart attack drug, ReoPro, on the other hand, is split 50-50 with marketing partner Eli Lilly & Co., of Indianapolis.
"I still think that the impact of this drug is not fully appreciated," Silverman said.
In other news, Centocor reported that ReoPro, in combination with stents or angioplasty, reduced the risk of death or heart attack significantly at the six-month follow-up mark in cardiac patients.
Centocor's stock (NASDAQ:CNTO) closed at $39.375, up $1.625. *