ABSTRACT: SEATTLE – In patients with early, active rheumatoid arthritis (RA), the primary endpoints from a Phase III study showed that Enbrel® (etanercept) slowed the progression of the disease and reduced the signs and symptoms. Enbrel was found to be generally well tolerated in this clinical trial. This announcement was made today by Immunex and Wyeth Ayerst, a division of American Home Products Corporation, the two companies that are co-marketing Enbrel in North America.
Detailed data regarding this clinical trial with a more complete analysis will be presented at a medical meeting in the future. The results described herein are based on investigational data analyzed by Immunex. These data have not been reviewed by the U.S. Food and Drug Administration (FDA) as part of an application for regulatory approval.
“The completion of this major study represents another significant milestone in the development of Enbrel,” said Peggy V. Phillips, senior vice president, pharmaceutical development, Immunex. “Based on the positive results of this study, Immunex intends to file a new supplemental biologics license application with the FDA seeking an expanded label for Enbrel to slow structural joint damage in patients with active RA and to improve the signs and symptoms of patients with early, active RA.”
The Phase III pivotal study evaluated 633 RA patients with early, active disease who received Enbrel or methotrexate, using two primary endpoints:
1. To study the ability of Enbrel to slow the progression of RA, the study utilized digitized x-ray data evaluation to monitor changes in joints. Structural damage to joints was measured over a one-year period using the Modified Sharp Scoring Method.
2. Signs and symptoms of RA were evaluated by the percent of improvement over six months.
All patients in this study had RA for less than three years and had never been treated with methotrexate. The study participants were randomized to receive either 25 mg or 10 mg of Enbrel, or up to 20 mg of methotrexate for 12 months. Patients received both Enbrel or placebo twice a week by subcutaneous injection and methotrexate or placebo once a week in pill form to ensure appropriate blinding of the trial.
The most common events reported in this trial in patients receiving Enbrel were mild to moderate injection site reactions that did not complicate treatment.
Enbrel was approved to treat moderately to severely active rheumatoid arthritis by the U.S. Food and Drug Administration (FDA) on November 2, 1998. Enbrel is currently indicated for the reduction in signs and symptoms of moderately to severely active rheumatoid arthritis in patients who have an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Immunex has filed a sBLA with the FDA, seeking approval for Enbrel to treat polyarticular course juvenile rheumatoid arthritis (JRA).
The first in a new class of rheumatoid arthritis (RA) drugs known as biologic response modifiers, Enbrel is an entirely new approach to the management of rheumatoid arthritis. Enbrel acts by binding tumor necrosis factor (TNF). TNF is one of the dominant cytokines or proteins that play an important role in the cascade of reactions that cause the inflammatory process of RA. Enbrel competitively inhibits the binding of TNF molecules to the TNF receptor (TNFR) sites. The binding of Enbrel to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
The most frequently reported adverse events in studies with Enbrel were mild to moderate injection site reactions. The long-term effects of Enbrel treatment, on the development or course of an active and/or chronic infection, malignancy and autoimmune disease are unknown. Patients with a serious infection, including sepsis, or who are allergic to Enbrel or any of its components should not take Enbrel. If patients develop an infection while on Enbrel, they should talk with their doctor immediately and be monitored closely. Enbrel should not be initiated in patients with active infections, including chronic or localized infections. Physicians should exercise caution in patients with a history of recurring infections or with underlying conditions, which may predispose them to infections, such as advanced or poorly controlled diabetes.
Immunex and Wyeth-Ayerst market Enbrel in North America. Other Wyeth-Ayerst affiliates will market Enbrel outside of North America. Additional information about Enbrel, including full prescribing information, can be found on the company-sponsored web site or by calling toll-free 1-888-4ENBREL (1-888-436-2735).