To print: Select File and then Print from your browser's menu

Title: FDA Approves Remicade (infliximab) as First and Only Biologic Treatment for Children With Active Crohn's Disease

"FDA Approves Remicade (infliximab) as First and Only Biologic Treatment for Children With Active Crohn's Disease"

Remicade Demonstrates Almost Ninety Percent Effectiveness at Week 10 HORSHAM, P.A. -- May 22, 2006 -- Centocor, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Remicade(R) (infliximab) for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active Crohn's disease (CD) who have had an inadequate response to conventional therapy. This approval establishes Remicade as the first and only biologic therapy approved for the treatment of pediatric Crohn's disease, a debilitating condition that causes inflammation of the gastrointestinal tract, typically resulting in symptoms such as diarrhea, fever, abdominal pain, weight loss and, in some sufferers, delayed development and stunted growth. Earlier this year, the supplemental Biologics License Application (sBLA) for Remicade for the treatment of pediatric CD was designated by the FDA for Priority Review. "Centocor is committed to providing therapeutic options with proven efficacy and an established safety profile for patients with a variety of conditions," said Jerome A. Boscia, MD, Senior Vice President, Clinical Research and Development, Centocor, Inc. "We are proud to broaden our patient base to the pediatric Crohn's population and will continue to advance research efforts to develop additional innovative therapeutic options for patients suffering from inflammatory conditions." The approval was based on data from the Phase 3 REACH (a Randomized, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of Anti-TNF Monoclonal Antibody Remicade in Pediatric Subjects with Moderate to Severe Crohn's Disease) trial which demonstrated that nearly 90 percent (88.4 percent) of pediatric patients with moderately to severely active Crohn's disease who had an inadequate response to conventional therapy achieved clinical response at week 10 when treated with Remicade. Additionally, the patients who responded to Remicade therapy were then randomized for maintenance therapy every 8 weeks or every 12 weeks. In the every 8 weeks maintenance treatment group, nearly two-thirds (64 percent) of the patients were in clinical response at one year and more than half were in clinical remission at the end of one year (56 percent). Along with this approval, Centocor, in consultation with FDA, has added to the boxed warning in the labeling for Remicade a description of rare post- marketing cases of hepatosplenic T-cell lymphoma that have been reported in adolescents and young adults with Crohn's disease (see Important Safety Information below and the full prescribing information available). Approximately 100,000 children under the age of 17 suffer from inflammatory bowel diseases (IBD), which include CD and ulcerative colitis (UC). The safety and efficacy of Remicade in the treatment of IBD in adults are well established. First approved in the United States for the treatment of adult CD in 1998, Remicade remains the only anti-tumor necrosis factor (TNF-alpha) therapy indicated for the treatment of Crohn's disease in both adults and pediatric patients. The FDA granted orphan drug designation to Remicade for the treatment of pediatric Crohn's disease on November 12, 2003. In addition, on August 30, 2004, a Remicade Phase 3 clinical development program for pediatric Crohn's disease was designated Fast Track by the FDA. In September of 2005, Remicade also was approved for the treatment of UC in adults. In addition to IBD, Remicade is approved for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. More than 700,000 patients have been treated with Remicade worldwide. "The approval of Remicade for this indication represents a significant breakthrough in therapeutic options for this underserved population and provides hope for children with moderate to severe pediatric Crohn's disease, which takes a heavy toll on their family, school and social lives," said Dr. Jeffrey Hyams, Head, Division of Digestive Diseases and Nutrition at Connecticut Children's Medical Center and Professor of Pediatrics at University of Connecticut School of Medicine. "Physicians who treat children with severe Crohn's disease should consider the risks and benefits of any medication versus the risks associated with inadequately treated disease." Clinical Trial Information: REACH In the REACH trial, 112 patients aged 6 to 17 years with moderately to severely active Crohn's disease despite treatments with an immunomodulator ą corticosteroids, received Remicade 5 mg/kg at weeks 0, 2 and 6. At week 10, 103 patients who had responded to Remicade therapy were randomized to receive Remicade maintenance treatments either every 8 weeks (n=52) or every 12 weeks (n=51) through week 46. Patients who lost response in the maintenance phase were eligible for a higher or more frequent dose of Remicade. Baseline demographic and disease characteristics were similar between groups. The median patient age was 13 years. Data from the REACH trial showed that 88 percent of patients treated with Remicade 5 mg/kg at 0, 2 and 6 weeks achieved the primary end point of the trial, clinical response at week 10, which was defined as a decrease from baseline of at least 15 points in the Pediatric Crohn's Disease Activity Index (PCDAI), and a total score of less than or equal to 30. Significantly more patients randomized to the Remicade maintenance regimen of one infusion every 8 weeks demonstrated clinical response and clinical remission at week 54 than those receiving Remicade maintenance every 12 weeks, a comparison made to better understand the pediatric dosing regimen. Sixty-three percent of patients (33 of 52) receiving Remicade every 8 weeks maintained clinical response after one year of treatment compared with 33 percent of patients (17 of 51) receiving maintenance therapy every 12 weeks ([P =.002). At 54 weeks, 56 percent of patients (29 of 52) receiving Remicade maintenance every 8 weeks were in clinical remission as assessed by a PCDAI score of less than or equal to 10, compared with 24 percent (12 of 51) in the every 12-week maintenance group (P <.001).

Additionally, some patients in the trial were able to reduce their corticosteroid dose. At baseline, the median average daily corticosteroid dose of randomized patients who were receiving corticosteroids was 0.3 mg/kg/day (q8 week group) or 0.6 mg/kg/day (q12 week group).

By their first maintenance visit (week 14 for the every 8-week group and week 18 for the every 12-week group), at least half of the patients had discontinued corticosteroids, an important step for many with Crohn's who experience side effects as a result of corticosteroid use. The median change from baseline in average daily corticosteroid use at week 54 for the combined q8 and q12 week maintenance treatment regimes was -0.27 mg/kg/day. The change from baseline in average daily corticosteroid dose was significant (P <.001).

In the REACH trial, patients were closely monitored, and the proportions of patients who experienced adverse events (AEs), serious adverse events (SAEs), serious infections, infusion reactions and immune responses was similar between the 8-week and 12-week Remicade maintenance groups.

Through the entire clinical trial, the most common SAEs were related to Crohn's disease. Infections were reported more frequently for subjects who received infusions every 8 weeks as opposed to every 12 weeks (73.6 percent and 38.0 percent, respectively), while serious infections were reported for 3 patients in the every 8-week and 4 patients in the every 12-week maintenance treatment group.

As reported by investigators, infections were primarily upper respiratory infections, such as the common cold. Three patients developed antibodies to infliximab, and nine patients in each maintenance group experienced an infusion reaction. No deaths, malignancies, reactivation of latent tuberculosis, neurological disorders or autoimmune disorders were noted. Overall, the AEs were consistent with those seen in previous trials in adult patients. Please see "Important Safety Information" below. Remicade has not been studied in patients with pediatric Crohn's disease six years of age or younger.

About Pediatric Crohn's Disease
Crohn's disease is a chronic illness that causes inflammation of the gastrointestinal tract, typically resulting in symptoms such as diarrhea, fever, abdominal pain and weight loss.

Children with Crohn's disease may also experience delayed development and stunted growth. Although it can involve any area of the gastrointestinal tract from the mouth to the anus, it most commonly affects the small intestine and/or colon.

About Remicade
Remicade is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA), ulcerative colitis (UC), and ankylosing spondylitis (AS). The safety and efficacy of Remicade have been well established in clinical trials over the past 13 years and through commercial experience with more than 700,000 patients treated worldwide.

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 reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric 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 reducing signs and symptoms in patients with active AS. In May 2005, Remicade was approved for reducing signs and symptoms of active arthritis in patients with PsA. Additionally, in September 2005, Remicade was approved 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 approval makes Remicade the first and only biologic approved for the treatment of moderate to severe UC.

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 (3 mg/kg), CD (5 mg/kg), PsA (5 mg/kg), and UC (5 mg/kg), 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 (5 mg/kg), Remicade is a two-hour infusion administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2 and 6.

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.

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. Children and young adults who have been treated for Crohn's disease with Remicade have developed a rare type of lymphoma that often results in death. These patients also were receiving drugs known as azathioprine or 6-mercaptopurine. 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 or if you have a lung disease called chronic obstructive pulmonary disease (COPD).

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.

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, Inc.

Copyright Š 2009 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content.