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REMICADE Granted Priority Review by U.S. Food and Drug Administration for Treatment of Ulcerative Colitis
31 May 2005
Centocor, Inc. announced today that the supplemental biologics license application (sBLA) for REMICADE® (infliximab) for the treatment of ulcerative colitis (UC) has been designated for priority review by the U.S. Food and Drug Administration (FDA). In Phase III clinical trials, REMICADE was studied as a monotherapy to evaluate its impact on clinical response, clinical remission and mucosal healing in patients with moderately-to-severely active UC, a gastrointestinal disorder that affects more than one-half million Americans. Currently, there are no FDA-approved therapies to treat moderately-to-severely active UC, a condition that may cause patients to face surgical removal of the colon, otherwise known as a colectomy. REMICADE is the only biologic indicated for the treatment of Crohn's disease (CD), another difficult-to-treat inflammatory bowel disease (IBD).
Priority review designation is granted by the FDA to products that are considered to be a potential therapeutic advance over current therapies. Centocor submitted the sBLA for REMICADE for UC to the FDA in March 2005, based on data from the ACT 1 and ACT 2 clinical trials. Data from ACT 1 and ACT 2 were presented for the first time at the 36th Annual Digestive Disease Week®, May 14-19, 2005.
ACT 1 and ACT 2, two pivotal Phase III clinical trials conducted to evaluate the safety and efficacy of REMICADE in people with active UC, show REMICADE 5 mg/kg and 10 mg/kg met predefined primary and secondary endpoints in each trial. These endpoints included measures of clinical response and remission in patients with active UC as well as quality of life measurements. In these trials, 62-69 percent of the patients in the infliximab groups showed significant improvement in their symptoms at week 8, with results of similar magnitude being reported in both the 5 mg/kg and 10 mg/kg groups. 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 adverse events reported in these trials, including serious adverse events, were similar to those reported in previous clinical experience with REMICADE clinical trials (see Important Information for Patients below).
"We are extremely pleased by the results of ACT 1 and ACT 2," said Dr. Jerome A. Boscia, senior vice president, Clinical Research and Development, Centocor. "REMICADE, if approved for the treatment of UC, would represent a major breakthrough for patients with this serious disease. We look forward to working closely with the FDA as it reviews these data for approval."
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 to 12) and an endoscopy score greater than 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 less than 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 less than 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 less than 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 less than 0.001). 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 less than 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 less than 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 less than 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 less than 0.001 for both). Clinical remission was achieved at week 8 in 34 percent and 28 percent of REMICADE 5 mg/kg and 10 mg/kg patients, respectively, compared to 6 percent of placebo-treated patients (P less than 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 less than 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 less than 0.001 for both). Mucosal healing at week 30 was achieved in 46 percent and 57 percent of patients receiving REMICADE 5 mg/kg and 10 mg/kg, respectively, compared to 30 percent of placebo-treated patients (P=0.009 and P less than 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 less than 0.001, respectively).
About UC
UC, a chronic inflammatory bowel disease affecting nearly 500,000 people in the U.S., is marked by the inflammation and ulceration of the colon mucosa, or innermost lining, which causes bloody stools, severe diarrhea and frequent abdominal pain. Tiny open sores, or ulcers, form on the surface of the lining where they bleed and produce pus and mucus. Because the inflammation makes the colon empty frequently, symptoms often lead to unwanted weight loss, blood loss and a host of secondary complications. UC is a chronic disease, and there is no cure. Although progress has been made in IBD research, investigators do not know what causes this disease.
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 (AS) in the U.S.
Earlier this month, the FDA approved REMICADE to reduce the signs and symptoms of active arthritis in patients with 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, CD and psoriatic arthritis, 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 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-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 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.
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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Contact:
Centocor, Inc.
Michael Parks, 215-325-4010
Mobile: 215-983-8000
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Source: Centocor, Inc.
Source: Business Wire
All trademarks and copyrighted information contained herein are the property of their respective owners.
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