Remicade gets broader indication in EU

Labeling cites improvement in physical function and reduction in rate of progression of joint damage in patients with rheumatoid arthritis

Schering-Plough Corp. (Kenilworth, NJ) and Centocor Inc. (Malvern, PA) announced that the European Union's (EU) Commission of the European Communities has granted marketing authorization to Remicade (infliximab) with methotrexate for the improvement in physical function of patients with rheumatoid arthritis and a reduction in the rate of the progression of joint damage when the response to disease-modifying drugs, including methotrexate, has been inadequate.

Commission approval of the centralized Type II variation for Remicade results in a single Marketing Authorization with unified labeling that is immediately valid in all 15 EU-Member States. The approval follows a positive recommendation by the EU's Committee for Proprietary Medicinal Products (CPMP) of the European Agency for the Evaluation of Medicinal Products (EMEA) in October 2000.

Roch F. Doliveux, president, Schering-Plough International, said, "With this approval, Remicade is now available for the treatment of three critical aspects of rheumatoid arthritis—signs and symptoms, improvement in physical function and a reduction in the rate of joint damage—providing patients with an immediate benefit by reducing pain and increasing physical function. The positive clinical outcomes demonstrated with Remicade show that treating rheumatoid arthritis patients with this therapy can provide a substantial benefit to sufferers of this debilitating disease and to society in terms of lost productivity," he added.

Remicade is currently marketed in the EU for rheumatoid arthritis, following the European Commission granting centralized marketing authorization in June 2000 to Remicade with methotrexate for the reduction of the signs and symptoms of rheumatoid arthritis in patients with active disease when the response to disease-modifying drugs, including methotrexate, has been inadequate. Remicade is also marketed in the EU for the treatment of Crohn's disease, a serious gastrointestinal disorder.

Centocor has exclusive marketing rights to Remicade in the United States. Schering-Plough has rights to market Remicade in all other countries throughout the world, except in Japan and parts of the Far East where the product will be marketed by Tanabe Seiyaku Ltd.

The centralized Type II variation application for Remicade for the improvement of physical function and the reduction in the rate of the progression of joint damage in rheumatoid arthritis patients is based on 54-week and 102-week radiographic (x-ray) data from ATTRACT (Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy), a double-blind, placebo-controlled, randomized clinical trial involving 428 patients at 34 clinical sites in North America and Europe. Structural joint damage (erosions and joint space narrowing) in both hands and feet was measured by the change from baseline in the total van der Heijde-modified Sharp score (0-440). The Health Assessment Questionnaire (HAQ; scale 0-3) was used to measure patients' average change from baseline scores over time in physical function. Based on x-ray data from the ATTRACT trial, a reduction in the rate of the progression of structural joint damage was observed in all infliximab groups at 54 weeks. The effects observed at 54 weeks were maintained through 102 weeks.

ATTRACT, one of the largest clinical studies ever conducted in patients with advanced rheumatoid arthritis, studied the safety and efficacy of Remicade at 30, 54, and 102 weeks. All treated patients had active disease despite methotrexate treatment. At week 54, a higher percentage of patients in all infliximab-treated groups had a significant reduction in signs and symptoms compared with methotrexate alone. This response was seen as early as two weeks and was maintained through 102 weeks of treatment. The approved dose is for the lowest dose studied in ATTRACT—3 mg/kg at zero, two and six weeks, then every eight weeks thereafter.

Patients enrolled in the ATTRACT trial were characterized as having disease that was particularly difficult to manage. The median duration of disease in trial patients was 8.4 years, and all patients were receiving methotrexate therapy. Half of the trial patients had been on methotrexate for three or more years. More than one-third of all patients had previous joint surgery, and half were classified as functional class 3 or 4, which indicates progressive and advanced disease.

The one-year results from ATTRACT indicate that Remicade was generally well tolerated. The most common adverse events in the ATTRACT trial included upper respiratory tract infections, headache, nausea, sinusitis, diarrhea, cough and rash. There was no increased incidence of serious adverse events (17% with Remicade and methotrexate versus 21% with methotrexate alone) or serious infections (6% with Remicade plus methotrexate versus 8% with methotrexate alone). The incidence of infusion reactions in patients receiving Remicade plus methotrexate (4%) was comparable to that in patients receiving methotrexate alone (2%).

In the United States, Remicade was approved by the U.S. Food and Drug Administration (FDA) in November 1999 for use in combination with methotrexate for the treatment of rheumatoid arthritis patients who have had an inadequate response to methotrexate. In January 2001, the FDA approved Remicade in combination with methotrexate to inhibit the progression of joint damage in patients with rheumatoid arthritis. Remicade is also marketed in the United States for the short-term treatment of active and fistulizing Crohn's disease.

Remicade is the first of a new class of agents approved for both rheumatoid arthritis and Crohn's disease that neutralizes a key inflammatory mediator called TNF-alpha. Overproduction of TNF-alpha leads to inflammation in chronic autoimmune conditions such as rheumatoid arthritis and Crohn's disease. It is believed that Remicade reduces inflammation in patients with rheumatoid arthritis by binding to and neutralizing TNF-alpha on the cell membrane and in the blood.

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. Its products, developed primarily through monoclonal antibody technology, help physicians deliver innovative treatments to improve human health and restore patients' quality of life. For more information about Remicade, visit Centocor's website at www.centocor.com. Centocor is a wholly owned subsidiary of Johnson & Johnson, a worldwide manufacturer of healthcare products.

Schering-Plough Corp. is a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide.

For more information, contact Denise K. Foy of Schering-Plough at 908-298-7616.

Source: Schering-Plough Corp.