SOURCE: Centocor

May 16, 2005 10:05 ET

REMICADE® Shows Efficacy in Treatment of Ulcerative Colitis in Phase III Clinical Trials

First Biologic to Show Efficacy in Two Debilitating Inflammatory Bowel Diseases, Crohn's Disease and Ulcerative Colitis

CHICAGO, IL -- (MARKET WIRE) -- May 16, 2005 -- Results from two Phase III trials presented today at Digestive Disease Week® 2005 reveal that, among patients with moderate to severe, active ulcerative colitis (UC) who experienced an inadequate response to conventional therapy, nearly 70 percent of patients at week 8 demonstrated significant improvement in their symptoms with REMICADE® (infliximab) therapy. Data from the ACT 1 and ACT 2 clinical trials show REMICADE met primary and secondary endpoints of clinical response, clinical remission and mucosal healing. Currently, there are no biologic therapies approved to treat moderate to severe UC, and with limited alternative treatment options, some patients face surgical removal of the colon, otherwise known as a colectomy.

"There is a need for efficacious therapies for patients with active UC who have an inadequate response to current treatments," said William Sandborn, MD, professor of medicine, Mayo College of Medicine; head, Inflammatory Bowel Disease Interest Group; director, IBD Clinical Research Unit, Mayo Medical Center. "While current treatments can relieve symptoms, many patients may still experience disease flares. The findings from both ACT 1 and ACT 2 reaffirm our hope that, with REMICADE therapy, we may be able to provide much-needed relief to those suffering from this debilitating illness."

An application for the approval of REMICADE to treat moderate to severe UC was submitted in the United States in March 2005. In December 2004, Centocor announced that REMICADE received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of active UC, an inflammatory bowel disease that affects nearly a half-million people in the United States. Fast Track Designation is applied to development programs for products that may treat serious or life-threatening diseases and address an unmet medical need. Based on these data from ACT 1 and ACT 2, REMICADE may now be eligible for FDA Priority Review (six-month versus standard 10-month review).

The ACT 1 and ACT 2 clinical trials were conducted to evaluate the safety and efficacy of REMICADE 5 mg/kg and 10 mg/kg at weeks 0, 2 and 6 and then every 8 weeks in people with active UC. The primary endpoint for these trials was a clinical response at week 8, defined as a decrease from baseline in the Mayo score by greater than or equal to 30 percent and greater than or equal to 3 points, accompanied by a decrease in the rectal bleeding subscore of greater than or equal to 1 or a rectal bleeding subscore of 0 or 1 at week 8. Secondary endpoints also included a clinical response at week 30, clinical remission at week 8 and week 30 and mucosal healing at week 8. The serious adverse events reported in these trials were similar to those reported in previous REMICADE clinical trials. (see Important Information below).

About ACT 1 and ACT 2

Two randomized, placebo-controlled trials, ACT 1 and ACT 2, were designed to evaluate the safety and efficacy of REMICADE for active UC. For 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 endoscopic evidence of moderate or severe UC (total Mayo score of 6 to12) and an endoscopy score greater than or equal to 2. For both trials, patients were randomized to receive placebo or REMICADE 5 mg/kg or 10 mg/kg. ACT 1 patients received study agent at weeks 0, 2 and 6 and then every 8 weeks through week 46 and had their last evaluation at week 54. ACT 2 patients received study agent at weeks 0, 2, and 6 and then every 8 weeks through week 22 and had their last evaluation 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=0.002, 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=0.002). 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 and P < 0.001). Mucosal healing was achieved at week 8 in 62 percent and 59 percent of patients receiving REMICADE 5 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=0.003 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=0.009 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).

About Digestive Disease Week

Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 14-19, 2005 in Chicago. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

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 RA and Crohn's disease 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 rheumatoid arthritis (RA). REMICADE is the only biologic indicated for the treatment of patients with moderately-to-severely active Crohn's disease (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.

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 eight 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 AS, 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 a million patients treated worldwide.

Important Information for Patients

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 where people taking REMICADE have developed severe liver problems. Signs that you could be having a problem include: jaundice (skin and eyes turning yellow), dark brown-colored urine, right-sided abdominal pain, fever, and severe fatigue (tiredness). You should contact your doctor immediately if you develop any of these symptoms. 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 lymphoma (a type of cancer) in patients on REMICADE and other TNF blockers are rare but occur more often than in the general population. Tell your doctor if you have or have had cancer. 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. Please read important information about REMICADE, including full prescribing information, at www.remicade.com.

About Centocor

Centocor is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield long-term benefits for patients and the healthcare community. The company is dedicated to the research and development of treatments for a wide range of diseases including cancer, infectious diseases, cardiovascular and metabolic diseases and Immune-Mediated Inflammatory Disorders (I.M.I.D.), such as arthritis and inflammatory skin diseases. Centocor's products, developed primarily through monoclonal antibody technology, help physicians deliver innovative treatments to improve human health and restore patients' quality of life. Centocor is a wholly owned subsidiary of Johnson & Johnson, the worldwide manufacturer of healthcare products.

Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States. Schering-Plough Corporation has rights to market REMICADE in all countries outside of the United States, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd. markets the product.

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