SEATTLE – Immunex Corporation announced today that the company has filed a supplemental biologics license application (sBLA) with the U.S. Food and Drug Administration (FDA) for Enbrel ® (etanercept), seeking a new label for the drug to slow structural damage and to improve the signs and symptoms of early, active RA.
“Irreversible damage can occur as early as two years into the disease process of rheumatoid arthritis, making early diagnosis and proper treatment absolutely essential,” said Scott W. Baumgartner, MD, an Enbrel clinical investigator.
The FDA approved Enbrel on November 2, 1998 to treat moderately to severely active rheumatoid arthritis in patients who have an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). The FDA included children and teen-agers (age 4-17 years) in the Enbrel label when it granted the drug a new indication on May 28, 1999 for the treatment of moderately to severely active polyarticular-course juvenile rheumatoid arthritis.
This new filing for Enbrel to slow the progression of rheumatoid arthritis and to treat the signs and symptoms of early, active RA is based on the results of a recently completed Phase III clinical trial, the summary results of which were announced in May 1999. The primary endpoints of this study showed that Enbrel may slow the progression of the disease and reduce the signs and symptoms. Enbrel was found to be generally well tolerated in this clinical trial. The most common events reported in this trial in patients receiving Enbrel were mild to moderate injection site reactions (34 percent) that did not complicate treatment.
A complete analysis will be presented at an upcoming major medical meeting. The results described herein are based on investigational data analyzed by Immunex. These data have not yet been reviewed by the U.S. Food and Drug Administration (FDA), but are included as part of the application for regulatory approval submitted today.
The Phase III pivotal study evaluated 632 RA patients for one year. 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 methotrexate, which was rapidly dose escalated to 20 mg per week. 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 two primary endpoints studied were the ability of Enbrel to:
1) Slow the progression of RA as measured by digitized x-rays to monitor changes in joints.
2) Reduce signs and symptoms of RA as measured by numeric ACR response criteria over six months.
Enbrel: 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.
Discontinue Enbrel in patients with serious infections or sepsis. Do not start Enbrel in the presence of sepsis, infection (including chronic or localized), or allergy to Enbrel or its components. Use caution in patients predisposed to infection. Closely monitor new infections during ENBREL treatment. In post-marketing use, serious infections including sepsis and death have been reported. Long-term effects of Enbrel on the development or course of infections, malignancy, and autoimmune disease are unknown. The most frequent adverse events in adult clinical trials were injection site reactions (ISR) (37 percent), infections (35 percent), and headache (17 percent). Malignancies were rare (<1 percent). Only the rate of ISR was higher than placebo. In children, infections (62 percent), headache (19 percent), abdominal pain (19 percent), vomiting (13 percent) and nausea (9 percent) occurred more frequently than in adults. The types of infections reported in JRA patients were generally mild and consistent with those commonly seen in outpatient pediatric populations.