Special To BioWorld Today
Centocor Inc.'s monoclonal antibody-based Remicade, already marketed for Crohn's disease, showed statisticallysignificant improvements in rheumatoid arthritis (RA) symptoms in a 30-week Phase III trial.
Results will form the basis of a new drug application (NDA), expected to be filed in December or January, Centocor spokesmanChristopher Allman said. The FDA approved Remicade for Crohn's disease in August.
"The [new] results show that inhibiting tumor necrosis factor-alpha is important in potentially managing a number of diseasesthat have an inflammation component," Allman told BioWorld Today. Adding RA as an indication "speaks to theinfrastructure we've developed at Centocor. We've evolved from being a research shop to a fully integrated company," he added.
Centocor, of Malvern, Pa., began shipping Remicade to distributors at the end of September.
The pivotal study in RA was called ATTRACT, which stands for Anti-TNF Trial in Rheumatoid Arthritis with ConcomitantTreatment. It included 428 patients in North America and Europe and five trial arms, each including standard therapy of theimmunosuppressant methotrexate. The arms consisted of 3 mg/kg of Remicade every four weeks or every eight weeks, 10 mgof drug in the same time periods, or placebo. Signs and symptoms of disease were reduced 52 percent in the drug groups ascompared 20 percent in the placebo group.
That 52 percent vs. 20 percent reduction was based on ACR 20 measurements, an assessment that represents a 20 percentreduction in the number of tender and swollen joints as well as patient and physician scoring, and a laboratory marker of painand inflammation. ACR 50 and ACR 70 scores, representing 50 and 70 percent reductions respectively, also were assessed.
Results showed 28 percent of Remicade patients achieved an ACR 50 response compared to 5 percent of placebo patients.Twelve percent of Remicade patients achieved ACR 70 compared to none on placebo. Swollen joints were reduced in the druggroups by 57 percent compared to 20 percent for placebo, and tender joints were reduced 61 percent for drug patientscompared to 26 percent with placebo.
The 3 mg/kg infusion very eight weeks was deemed the optimal dose. Patients were those evaluated to have disease that wasdifficult to manage, with most having been on methotrexate therapy for three or more years. About half had progressive andadvanced disease.
Centocor World's Top Monoclonal Antibody Producer
"It's important that what sets Remicade apart is that it is a monoclonal antibody, and that is a business platform forCentocor," Allman said. "We're the largest producers of monoclonal antibodies in the world. There is a cost saving, when youuse monoclonal antibodies like Remicade and ReoPro."
ReoPro is approved for heart attack uses and is being studied in a variety of related indications. Early stage Remicade studiesare under way or being planned for the additional indications of psoriasis, asthma, ulcerative colitis and multiple myeloma.
Centocor has retained U.S. rights for Remicade for all indications. Schering-Plough Corp., of Madison, N.J., has rightseverywhere outside the U.S. except Japan and the Far East, where they are held by Osaka-based Tanabe Seiyaku Co. Ltd.
Remicade has not yet been approved outside the U.S. for Crohn's disease, though approval in Europe could occur early in 1999,Allman said. International filings for RA would follow U.S. submissions, he said.
Initial data were presented Monday at the American College of Rheumatology meeting in San Diego, with more detail expectedThursday.
Centocor's stock (NASDAQ:CNTO) closed Monday at $51.625, up $4.375.