FDA Approves Remicade to Treat Ulcerative Colitis

HORSHAM, Pa., September 16, 2005 -- Centocor, Inc. announced today that Remicade (infliximab) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ulcerative colitis (UC), making Remicade the first and only biologic approved for UC, a chronic inflammatory bowel disease (IBD).

Remicade is now indicated for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. This is an unprecedented milestone in the treatment of moderate-to-severe UC; to date, no therapy has ever been indicated for mucosal healing and eliminating the use of corticosteroids.

"The approval of Remicade for the treatment of UC represents a major breakthrough for patients suffering from this often debilitating disease," said William J. Sandborn, M.D., professor of medicine, Mayo Clinic College of Medicine and head of the IBD Interest Group and director of the IBD Clinical Research Unit at Mayo Medical Center. "Not only did many patients in clinical trials experience a significant reduction in the occurrence of symptom flare- ups with Remicade, some achieved clinical remission and mucosal healing as well. This is welcome news for these patients whose only option otherwise may have been surgery to remove their colons."

Remicade’s efficacy in the treatment of IBD is well established. First approved in the United States for the treatment of Crohn’s disease (CD) in 1998, Remicade remains the only anti-tumor necrosis factor (TNF-alpha) therapy indicated for the treatment of CD. With this new approval for the treatment of ulcerative colitis, Remicade is now the only biologic indicated for the treatment of both types of inflammatory bowel diseases, CD and UC.

In addition to UC and CD, Remicade is also indicated for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. More than 600,000 patients have been treated with Remicade worldwide. This new approval for the treatment of UC continues to demonstrate the benefit of Remicade across immune-mediated inflammatory diseases.

UC is a debilitating chronic disease affecting more than 500,000 Americans, for whom there is no medical cure, and while UC affects more people in the United States than multiple sclerosis or cystic fibrosis, general awareness of the disease is lower. Characterized by inflammation and ulceration of the inner lining of the colon, UC symptoms can often include unwanted weight loss, severe - sometimes uncontrollable - bloody diarrhea, fatigue and frequent abdominal pain. For some patients, symptoms may lead to surgical removal of the colon or to secondary complications such as colorectal cancer.

"We are optimistic that the use of a treatment like Remicade will provide many people with relief from the debilitating symptoms that have had such a profound impact on their lives," said Rodger DeRose, president and CEO of the Crohn’s & Colitis Foundation of America. "Results from a recent patient survey revealed that UC affects many aspects of people’s lives, from their relationships with families and employers to the ability to participate in social activities."

Clinical Trial Information: ACT 1 and ACT 2

The approval of Remicade is based on positive results seen in two randomized, placebo-controlled pivotal Phase 3 clinical trials, ACT 1 and ACT 2, which were conducted to evaluate the safety and efficacy of Remicade in people with active, moderate-to-severe UC.

In each trial, 364 patients with active UC who were unresponsive to at least one standard therapy - including corticosteroids, immunosuppressants or 5-ASAs - were enrolled. Patients in ACT 1 and ACT 2 had evidence of moderate or severe UC (total Mayo score of 6 to 12 and an endoscopy score greater than or equal to 2). In both trials, patients were randomized to receive placebo or Remicade 5 mg/kg or 10 mg/kg. ACT 1 patients received the study agent at weeks 0, 2 and 6 and then every 8 weeks through week 46 and had their last evaluations at week 54. ACT 2 patients received the study agent at weeks 0, 2 and 6 and then every 8 weeks through week 22 and had their last evaluations at week 30.

In ACT 1, significantly higher proportions of patients receiving Remicade 5 mg/kg (69 percent) and 10 mg/kg (62 percent) achieved clinical response at week 8 versus placebo-treated patients (37 percent; P<0.001 for both). In addition, at week 30, 52 percent of patients in the 5 mg/kg and 51 percent of patients in the 10 mg/kg Remicade treatment group were in clinical response versus 30 percent of placebo-treated patients (P<0.001 and P<0.01, respectively). At week 8, 39 percent and 32 percent of patients treated with Remicade 5 mg/kg and 10 mg/kg, respectively, were in clinical remission compared to 15 percent of placebo-treated patients (P<0.001 and P<0.01). These differences in remission rates persisted at week 30 (34 percent, 5 mg/kg; 37 percent, 10 mg/kg versus 16 percent, placebo; P<0.001 for both). Mucosal healing was achieved at week 8 in 62 percent and 59 percent of patients receiving Remicade 5 mg/kg and 10 mg/kg, respectively, versus 34 percent of placebo-treated patients (P<0.001). This difference in mucosal healing was maintained at week 30 (50 percent, 5 mg/kg; 49 percent, 10 mg/kg versus 25 percent, placebo; P<0.001 for both). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was greater in both Remicade groups compared to the placebo group (24 percent, 5 mg/kg; 19 percent, 10 mg/kg; 10 percent, placebo; P=0.030 and P=0.125, respectively).

In ACT 2, significantly higher proportions of patients receiving Remicade 5 mg/kg (65 percent) and 10 mg/kg (69 percent) were in clinical response at week 8 versus 29 percent who received placebo (P<0.001 for both). At week 30, 47 percent of patients receiving Remicade 5 mg/kg and 60 percent receiving 10 mg/kg were in clinical response versus 26 percent of patients receiving placebo (P<0.001 for both). Clinical remission was achieved at week 8 in 34 percent and 28 percent of Remicade 5 and 10 mg/kg patients, respectively, compared to 6 percent of placebo-treated patients (P<0.001 for both). Differences in remission rates persisted at week 30 (26 percent, 5 mg/kg; 36 percent, 10 mg/kg; 11 percent, placebo; P<0.01 and P<0.001). Mucosal healing was achieved at week 8 in 60 percent and 62 percent of patients receiving Remicade 5 mg/kg and 10 mg/kg, respectively, compared to 31 percent of placebo-treated patients (P<0.001 for both). Mucosal healing at week 30 was achieved in 46 percent and 57 percent of patients receiving Remicade 5 and 10 mg/kg, respectively, compared to 30 percent of placebo-treated patients (P<0.01 and P<0.001). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was significantly greater in both Remicade groups compared with the placebo group (18 percent, 5 mg/kg; 27 percent, 10 mg/kg; 3 percent, placebo; P=0.010 and P<0.001, respectively).

The serious adverse events reported in these trials were similar to those reported in previous Remicade clinical trials. (See Important Safety Information below).

About Remicade

Remicade is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and the only agent approved for the treatment of both rheumatoid arthritis (RA) and CD in North America, the EU and Japan. In the U.S., Remicade, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active RA. Remicade is the only biologic indicated for the treatment of patients with moderately-to-severely active CD who have had an inadequate response to conventional therapy. Remicade is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing CD. In December 2004, Remicade was approved for the treatment of active ankylosing spondylitis in the U.S. On May 13, 2005, Remicade was approved for the treatment of psoriatic arthritis.

Remicade is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to inject themselves frequently, Remicade is the only anti-TNF biologic administered directly by caregivers in the clinic or office setting. In RA and CD, Remicade is a two- hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6. As a result, Remicade patients may require as few as six treatments each year. In ankylosing spondylitis, Remicade is a two-hour infusion (5 mg/kg) administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. The safety and efficacy of Remicade have been well established in clinical trials over the past 12 years and through commercial experience with over a half-million patients treated worldwide.

Important Safety Information

Many people with heart failure should not take Remicade; so prior to treatment you should discuss any heart condition with your doctor. Tell your doctor right away if you develop new or worsening symptoms of heart failure (such as shortness of breath or swelling of your ankles or feet). There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia. Some of these infections have been fatal. Tell your doctor if you have had recent or past exposure to people with TB. Your doctor will evaluate you for TB and perform a skin test. If you have latent (inactive) TB, your doctor should begin TB treatment before you start Remicade. Remicade can lower your ability to fight infections, so if you are prone to or have a history of infections, or develop any signs of an infection such as fever, fatigue, cough, or the flu while taking Remicade, tell your doctor right away. Also tell your doctor if you have lived in a region where histoplasmosis or coccidioidomycosis is common.

There have been rare cases of serious liver injury in people taking Remicade, some fatal. Contact your doctor immediately if you develop symptoms such as jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe fatigue.

Blood disorders have been reported, some fatal. Tell your doctor if you develop possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking Remicade. Nervous system disorders have also been reported. Tell your doctor if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, or visual disturbances while taking Remicade.

Reports of a type of blood cancer called lymphoma in patients on Remicade or other TNF blockers are rare but occur more often than expected for people in general. People who have been treated for rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, or psoriatic arthritis for a long time, particularly those with highly active disease may be more prone to develop lymphoma. Cancers, other than lymphoma, have also been reported. If you take Remicade or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should also tell your doctor if you have had or develop lymphoma or other cancers while you are taking Remicade.

Serious infusion reactions have been reported with Remicade, including hives, difficulty breathing, and low blood pressure. Reactions have occurred during or after infusions. In clinical studies, some people experienced the following common side effects: respiratory infections (that may include sinus infections and sore throat), coughing, and stomach pain or mild reactions to infusion such as rash or itchy skin.

Source: Centocor

Posted: September 2005


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