Therapeutic Breakthrough For Rheumatoid Arthritis Becomes First Biologic Response Modifier Approved To Treat Children And Teen-Agers With JRA
SEATTLE - ENBREL® (etanercept) was approved today by the U.S. Food and Drug Administration (FDA) for the treatment of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in patients who have had an inadequate response to one or more disease modifying medicines. Today's announcement was made by Immunex Corporation (NASDAQ: IMNX) and Wyeth-Ayerst Pharmaceuticals, a division of American Home Products Corporation (NYSE: AHP), the companies who market ENBREL in North America.
JRA is an autoimmune system disease that strikes children before age sixteen and can cause painful joint swelling, deformity, stunted growth and increased mortality. According to the Arthritis Foundation, JRA affects approximately 50,000 children in the United States. The disease can impair a child's ability to take part in physical activities, make daily activities such as schoolwork more difficult, and affect a child's physical appearance.
"I never thought my daughter would be able to get out of bed in the morning without experiencing extreme pain, much less attend school with her peers on a daily basis," said Erite Freed, the mother of a 15-year-old girl, Lauren Blumenthal, with JRA who participated in the ENBREL JRA clinical trial. "ENBREL has had a dramatic effect on my daughter's life."
"Children with JRA face the possibility of a lifetime of pain and disability," said Daniel J. Lovell, M.D., M.P.H., a pediatric rheumatologist at Children's Hospital Medical Center of Cincinnati and principal investigator of the clinical study on which the JRA indication was based. "Rheumatologists have had limited options to treat children with moderate to severe arthritis. The approval of ENBREL for JRA opens a new era of hope for these children, teen-agers and their families."
Prior to this approval, ENBREL was already approved by the FDA for the treatment of moderately to severely active rheumatoid arthritis in adults. ENBREL has been granted orphan drug designation by the FDA for the treatment of JRA. Orphan drug designations are given to drugs for the treatment of medical conditions affecting 200,000 people or less in the United States.
ENBREL (etanercept) has been studied in more than 1,000 people with RA, including 69 JRA patients from ages 4 to 17 years. Seventy-four percent of the 69 study participants demonstrated a clinical response to ENBREL, measured by the JRA Definition of Improvement. The JRA Definition of Improvement includes a physician's assessment, a count of joints with active arthritis, a count of joints with loss of motion, a patient's or parent's global assessment, a functional ability test and a blood test to assess inflammation (ESR). ENBREL has not been studied in children younger than four years old.
The tolerability profile of ENBREL in JRA patients was similar to that seen in adult RA patients treated with the drug. ENBREL should not be started in patients who have an active or serious infection or are allergic to ENBREL or its ingredients. If a patient develops a new infection while on ENBREL, they should tell their doctor right away. In adult medical studies some patients experienced injection site reactions (37 percent), infections (35 percent), headache (17 percent), and malignancies (less than 1 percent). With the exception of injection site reactions, the adverse event rate over time was similar for patients receiving ENBREL or 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.
The long-term effects of ENBREL treatment on infection, malignancy or autoimmune disease are unknown. Since the introduction of ENBREL, there have been some reports of infection that have led to serious problems, including fatalities. Many of these reports have been in people with other diseases, like diabetes, which make them more likely to get serious infections.
"It is very gratifying to achieve this important milestone -- approval of the first biologic therapy for the treatment of moderately to severely active polyarticular course JRA," said Peggy V. Phillips, Immunex senior vice president, pharmaceutical development and general manager, ENBREL. "We want to thank the investigators, patients, and Food and Drug Administration officials who worked with us to extend this important new therapy to the thousands of children who suffer from this potentially devastating and chronic disease."
"This is an important milestone for the JRA community as well as Immunex and Wyeth-Ayerst Pharmaceuticals," said Joseph M. Mahady, president, Wyeth-Ayerst, North America. "We are continuing to study ENBREL for treatment of rheumatoid arthritis as well as for other diseases."
The dosage of ENBREL for JRA patients is 0.4 mg/kg (maximum dose = 25 mg) given twice weekly as a subcutaneous injection 72 - 96 hours apart. A two-part clinical trial was conducted in patients ranging from 4 - 17 years of age with active polyarticular course JRA who were refractory to or intolerant of methotrexate therapy. In part 1 of the study, which lasted 3 months, all patients received ENBREL. Fifty-one of 69, or 74 percent, of these patients demonstrated a positive clinical response and entered part 2 of the study, which lasted an additional 4 months. In part 2 of the study, patients were randomized to receive either ENBREL or placebo. Only six of the 25 patients remaining on ENBREL experienced a disease flare (24 percent) compared to 20 of 26 of placebo patients who experienced a disease flare (77 percent).
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.
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 at (www.ENBREL.com) or by calling toll-free 1-888-4ENBREL (1-888-436-2735). Immunex manufactures ENBREL.
Immunex is a biopharmaceutical company dedicated to developing immune system science to protect human health. The company's products offer hope to patients with cancer, inflammatory and infectious diseases.
Wyeth-Ayerst, a division of American Home Products Corporation, is a major research-oriented pharmaceutical company with leading products in the areas of women's health care, cardiovascular disease therapies, central nervous system drugs, anti-inflammatory agents, vaccines and generic pharmaceuticals.
American Home Products owns a majority interest in Immunex. AHP is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of prescription drugs and over-the-counter medications. It is also a leader in vaccines, biotechnology, agricultural products and animal health care.
NOTE: This release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development, regulatory approvals, patent litigation, product commercialization and other risks described from time to time in the SEC reports filed by Immunex, including the most recently filed 10-K and 10-Q. For more information, please refer to www.immunex.com.