Expanded Use in U.S. Sought for REMICADE, Global Market Leader in Anti-TNF-a Therapies

Malvern, PA, April 19, 2004 – Centocor, Inc., announced today that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for the use of REMICADE® (infliximab) for the treatment of ankylosing spondylitis (AS), a chronic, progressive and debilitating inflammatory disease that often leads to stiffening and subsequent fusion of the spine. REMICADE is the global market leader among anti-tumor necrosis factor alpha (TNF-a) therapies and is the only biologic indicated for the treatment of both rheumatoid arthritis (RA) and Crohn’s disease (CD) in North America, the European Union and Japan. In May 2003, REMICADE was approved in the European Union for the treatment of ankylosing spondylitis, making it the first biologic to receive approval from a major regulatory authority for this use.

The U.S. submission for AS is based primarily on the results of the ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial, which showed that patients with active AS achieved improvement in signs and symptoms associated with their disease, including reduced spinal pain, increased physical function and increased health-related quality of life when treated with REMICADE.

“The ASSERT trial and this sBLA demonstrate our continued commitment to the research and development of REMICADE in the treatment of serious immune-mediated inflammatory disorders,” said Jerome A. Boscia, M.D., senior vice president, Clinical R & D, Centocor, Inc. “We are very encouraged by the clinical outcomes seen in the ASSERT trial and we hope this submission will help build a positive role for REMICADE in patients suffering from this progressive, debilitating disease.”

About ASSERT
ASSERT was a Phase III, randomized, placebo-controlled, double-blind, 30-center trial in North America and Europe. The trial included 279 patients; 201 patients were treated with REMICADE (infliximab) and 78 patients were given placebo infusions. Patients were given REMICADE monotherapy 5 mg/kg infusions at weeks 0, 2 and 6, followed by infusions every six weeks.

The primary endpoint of the trial was the proportion of patients demonstrating a 20 percent or greater improvement in signs and symptoms as measured by the ankylosing spondylitis assessment (ASAS 20) at 24 weeks. Patients were assessed at baseline and at 24 weeks by standard AS performance scores. In the infliximab group, 61 percent achieved ASAS 20 compared to placebo at 19 percent. The benefit seen in the REMICADE group was statistically significant (p < 0.001) compared to placebo. The response criteria measured by the ASAS 20 included patient global assessment, spinal pain, physical function and inflammation.

The most commonly reported adverse events were upper respiratory tract infections, which occurred at a slightly higher rate in the placebo group (15 percent) compared to the infliximab group (14 percent). Serious adverse events were noted in 3.5 percent of REMICADE treated patients compared to 2.7 percent of patients receiving placebo.

About Ankylosing Spondylitis
According to the Spondylitis Association of America (SAA), AS is a painful and progressive form of spinal arthritis that usually affects people under the age of 35 years. It typically begins in the late teens and early twenties and can result in fusing of the spinal vertebrae, hips and other joints. Often misdiagnosed as "just back pain" or undifferentiated arthritis, AS is a systemic inflammatory disease that in addition to its effect on the spine, can affect vision, internal organs, and peripheral joints. The SAA estimates that between 350,000 and one million people in the United States suffer from AS or a related disease.

Important 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) and sepsis. 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. If you are prone to or have a history of infections, currently have one, or develop one 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 or if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, or visual disturbances.

There are also reports of serious infusion reactions with hives, difficulty breathing, and low blood pressure. 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 REMICADE
REMICADE is a monoclonal antibody that specifically targets and irreversibly binds to tumor necrosis factor-alpha (TNF-a) on the cell membrane and in the blood. Overproduction of TNF-a is believed to play a role in RA, ankylosing spondylitis1 and Crohn’s Disease (CD), a serious gastrointestinal disorder, in addition to a wide range of Immune-Mediated Inflammatory Disorders (I.M.I.D.) in which REMICADE is currently being studied.

REMICADE is the only anti-TNF biologic therapy that has received marketing authorizations for the treatment of RA, CD and in the European Union, AS. In most countries where it has received marketing authorization, REMICADE, in combination with methotrexate, is indicated for the treatment of patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate alone. REMICADE is the only biologic indicated for the treatment of patients with moderately to severely active Crohn’s disease 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 Crohn’s disease.

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 patients, REMICADE is 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. The safety and efficacy of REMICADE have been well established in clinical trials conducted over the past 10 years and through commercial experience with more than 400,000 patients treated worldwide2.

Centocor discovered REMICADE and has exclusive marketing rights to the product in the United States. Schering-Plough markets 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.

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.

References:

1 Braun J, et al, Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens form patients with ankylosing spondylitis. Arthritis Rheum 1995; 38(4): 499-505.

2 Data on file at Centocor