WASHINGTON---The Food and Drug Administration today approved a revolutionary treatment for the debilitating bowel disorder, Crohn's disease. A biologically engineered antibody that attacks a protein responsible for much of the patients misery.
Centocor's infliximab is a part-human, part-mouse antibody, to be sold under the brand name Remicade.
About 400,000 Americans have Crohn's disease, a severe gastrointestinal-tract inflammation that causes diarrhea, abdominal pain, fever and weight loss. In severe cases, patients develop intestinal blockages and ulcerlike channels called fistulas that burrow through the bowel wall.
It mostly strikes women, usually between the ages 20 and 35. There is no cure. Most patients are treated with steroids to reduce the inflammation; some require repeated surgeries to remove damaged parts of the intestine.
Remicade is a monoclonal antibody, a biologically engineered drug that sweeps through the body hunting down and neutralizing tumor necrosis factor, a protein that causes much of the intestinal inflammation.
In a study of 108 moderate to severe Crohn's patients, 82 percent who received and injection of Remicade improved, including 48 percent who went into remission. That compares with 16 percent of patients who improved while taking a placebo.
In the worst case patients, Centocor says Remicade is the first medicine documented to heal fistulas: 68 percent had at least half of their ulcerlike sores close during therapy, vs. 26 percent of patients who received placebo injections.
However, the benefits wore off. Patients benefited most within the first two to four weeks after a single dose, the government said, and the percentages of patients who saw benefits then fell over the next few months.
As part of the drug's approval, Centocor agreed to study whether the drug also works over a longer period of time, and whether it is safe for long-term use, the government said. Side effects included hives, shortnes of breath or reduction of blood pressure during the drug's infusion. Patients also may suffer nausea, fatigue, and infection, the company warned.
Centocor says pharmacies should have supplies of Remicade by early October. A price was not immediately announced. Patients may also know the drug as Avakine, the name Centocor first used when testing it.
MALVERN, PA.--Oct. 13, 1998 -- Centocor, Inc.'s Remicade(TM) (infliximab) is now available in the United States for the treatment of Crohn's disease.
Remicade was cleared for marketing by the U.S. Drug and Food Administration Aug. 24, 1998, for the treatment of moderately to severely active Crohn's disease for the reduction of the signs and symptoms, in patients who have an inadequate response to conventional therapy. It is also indicated as a treatment for patients with fistulizing Crohn's disease for reduction in the number of draining enterocutaneous fistula(s).
Remicade is the first new product in 30 years indicated for this serious condition.
Remicade is the first of a revolutionary new class of agents that blocks activity of a key inflammatory mediator called tumour necrosis factor alpha (TNF-alpha).Overproduction of TNF-alpha leads to inflammation in conditions such as Crohn's, rheumatoid arthritis and other autoimmune diseases. It is believed that Remicade reduces intestinal inflammation in patients with Crohn's disease by binding to and neutralizing TNF-alpha on the cell membrane and in the blood.
In a clinical study, patients with moderate to severe Crohn's disease who did not respond to conventional therapy were treated with Remicade (5 mg/kg). Eighty two percent of Remicade-treated patients achieved a clinical response after 4 weeks compared to 16 percent of patients who received placebo. In addition, 48 percent of patients achieved clinical remission.
Remicade is the first product documented to reduce the number of open fistulas -- openings that burrow through the bowel wall, into nearby organs or through the surface of the skin -- in a controlled clinical trial.In one Phase III clinical study of 94 patients with fistulizing Crohn's disease, 68 percent of patients treated with Remicade (5 mg/kg) experienced closure of at least 50 percent of fistulas(s) for four weeks or more compared with 26 percent of placebo-treated patients. Over half (55 percent) experienced closure of all their fistula(s).
Approximately five percent of Crohn's disease patients studied discontinued Remicade treatment. The most common reasons for discontinuation were infusion reaction and infections. On rare occasions, these reactions were serious but resolved with standard treatment for hypersensitivity reactions or discontinuation of Remicade therapy. The most common adverse reactions occurring more frequently with Remicade than with placebo include nausea, upper respiratory tract infections and abdominal pain.
Remicade therapy may result in the development of autoantibodies. However, development of such autoantibodies rarely leads to clinical symptoms or discontinuation of therapy.
The above story reprinted with permission of The Doctor's Guide to the Internet(TM). Their URL is http://www.docguide.com
Give them a visit sometime.
Top Stories: Centocor Halts Remicade Trial on Safety Concern, Notifies Docs
By Jesse Eisinger Senior Writer 11/19/98 6:32 PM ET
Centocor (CNTO:Nasdaq) has halted a trial of Remicade in Crohn's disease patients due to safety concerns, and it has sent doctors a letter detailing the results.
In the trial, 25% of the 40 patients suffered side effects that appear to be related to immune-system reactions to the drug, generically known as infliximab, the letter says. Remicade was approved in August as a short-term treatment for moderate to severe Crohn's patients, who suffer from inflamed bowels
. Centocor is continuing to look at chronic treatment with the drug to establish long-term safety and effectiveness. Toward that end, the company started a trial six months ago, which was halted "recently," according to a company spokesman. After discussions with the Food and Drug Administration, Centocor notified doctors in what is known in the medical community as a "dear doctor" letter.
Asked why the company didn't disclose either the halting of the trial, spokesman Jason Rubin says, "We didn't think it was that significant an event." Of the company's decision not to disclose the dear doctor letter, Rubin says that Centocor discussed safety issues with the investment community at scientific meetings in recent weeks.
The drug was launched for short-term treatment on Oct. 1. Bulls expect the drug to reach sales of about $30 million this year, while bears think side-effects and weak demand will hold sales far lower. "That [$30 million] remains our target and so far we're off to a good start," says Jason Rubin, Centocor's spokesman. Centocor hopes to win approval for the drug in the much larger market of rheumatoid arthritis patients by this time next year. The company reported revenue of $235 million for the nine months ended Sept. 30.
Centocor stock's closed up 1 1/2 Thursday at 50 7/8 as bulls downplayed the letter's importance. For instance, Rubin, the spokesman, noted that the study involved a small number of patients.
The letter, dated Nov. 10, circulated around Wall Street Wednesday and Thursday, helping to push up the stock of competitor Immunex (IMNX:Nasdaq), which climbed 9 7/16, or 12%, Thursday to close at 86 15/16. The news is considered good for Enbrel, Immunex's drug for treating rheumatoid arthritis patients.
(Also boosting Immunex shares was a Nov. 12 quarterly filing with the Securities and Exchange Commission indicating that Immunex has committed to buy $104 million worth of Enbrel inventory from the contract manufacturer on the drug as of Sept. 30. To one long investor who asked to remain anonymous, that means the company and its marketing partner, American Home Products (AHP:NYSE), are a big first year for the drug, with sales of about $400 million. Also, a rumors circulated that American Home, Immunex's majority owner, might buy the rest of the company for north of 100 a share. Tim Warner, an Immunex spokesman, dismissed the takeout rumor as inaccurate.)
Worries about side effects have been Centocor's single greatest worry about the financial prospects for Remicade, which is an antibody against a natural immune-system protein called tumor necrosis factor. Of special concern is how many times patients can be treated with the drug before they either have an immune response or find that the effect has worn off.
The patients in the study had previously taken Remicade and were being tested to judge the effectiveness of re-treating them two to four years later. Of the 40 patients, 24, received an older, liquid formulation of the drug first, then the new powdered form. Nine of the 10 patients who suffered serious adverse events were given the older formulation initially and the new formulation on being re-treated. Of the 16 remaining patients who received the new formulation both initially and on re-treatment, only one suffered a serious adverse event. Nine of 10 patients had severe muscle pain; seven of 10 had rashes and six ran fevers. All the patients got better within three days.
In the letter, the company notes that "no similar set of delayed adverse events have been observed in other completed clinical trials involving 216 patients receiving 429 re-treatments at intervals ranging from one to 55 weeks." In an ongoing re-treatment study of rheumatoid arthritis patients, 340 subjects have been re-treated and "none of these patients have developed" similar side effects, the letter says. However, the rheumatoid arthritis patients were taking methotrexate, an immune suppressant, in conjunction with Remicade. One fund manager who owns Centocor says the older formulation might not be as pure as the new, giving rise to the serious adverse events. "I'm not panicked. When you look at Crohn's disease, it's so horrible and nothing else works for it," says the manager, who asked to remain anonymous. "But where it matters is competing with Immunex," adds the manager, figuring that American Home sales reps will make hay with the letter.
The above article reprinted with permission from TheStreet.com.