FDA accepts REMICADE® (infliximab) for the treatment of early rheumatoid arthritis

Centocor, Inc., announced today that the U.S. Food and Drug Administration (FDA) has accepted its filing of a supplemental Biologics License Application (sBLA) for REMICADE® (infliximab) as first-line therapy, in combination with methotrexate, for the treatment of early rheumatoid arthritis (RA) patients with moderately-to-severely active disease. REMICADE®, in combination with methotrexate, is currently indicated in the U.S. for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately-to-severely active RA who have had an inadequate response to methotrexate alone.

REMICADE® is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies, the only agent approved for the treatment of both RA and Crohn's disease in North America, the European Union and Japan, and was the first biologic approved for ankylosing spondylitis (AS) in the European Union.

The submission is based on the results of the ASPIRE (Active Controlled Study of Patients Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset) trial. In this trial, REMICADE® plus methotrexate was superior to the gold standard of methotrexate alone in the treatment of early RA patients who were methotrexate-naive. REMICADE® plus methotrexate was superior to methotrexate alone in inhibiting the progression of structural damage, preventing bone erosions, improving physical function and improving clinical symptoms. To date, no anti-TNF monotherapy or combination strategy has been proven superior to methotrexate alone in a clinical study comprised exclusively of early RA patients.

"Increasingly, clinical evidence supports that earlier therapy for RA may enhance patient benefit. This submission for REMICADE® represents Centocor, Inc.'s, continued leadership and commitment to advancing research that we believe may ultimately provide meaningful benefit to patients with early RA," said Jerome A. Boscia, M.D., senior vice president, clinical R&D, Centocor, Inc.

About Early Rheumatoid Arthritis

RA is a chronic, progressive disease, and research demonstrates that a critical therapeutic window exists within the first two years of disease onset when the rate of radiographic progression of the disease can be "reset"^1,2,3. Radiographic changes occur within two years of disease onset in 50-70 percent of RA patients⁴. The American College of Rheumatology (ACR) suggests control of disease progression should start early to limit joint damage in RA³. RA is associated with substantial disability and economic losses, and one study showed that one-third of patients in the UK who were employed became work-disabled within two years of disease onset⁵. Rheumatologic disorders also account for 25 percent of Social Security disability payments⁶.

About ASPIRE

ASPIRE was a 54-week, randomized, double blind, active control study involving 1,049 patients with early RA (less than or equal to three years duration) enrolled in 125 centers in North America and Europe evaluating the efficacy and safety of REMICADE® in combination with methotrexate compared to methotrexate alone. Patients in the ASPIRE study had an average of only seven months of disease duration and more than 80 percent already had evidence of erosive joint destruction. At randomization, all patients received methotrexate and either placebo, 3 mg/kg of REMICADE® or 6 mg/kg of REMICADE® at weeks zero, two and six and then every eight weeks thereafter. The ASPIRE trial had three co-primary endpoints at week 54: improvement of signs and symptoms, progression of structural damage and improvement in physical function. All three primary endpoints were met, with the REMICADE® regimen being superior to methotrexate alone on all primary and major secondary endpoints.

The most commonly reported adverse events were upper respiratory infection, nausea and headache. Serious adverse events reported were similar to those observed in controlled clinical trials and clinical experience with REMICADE® as described in the prescribing information.