Amgen and Wyeth Announce Enbrel Drug Gets Black Box Infection-Risk Warning
THOUSAND OAKS, Calif. & COLLEGEVILLE, Pa. -- Amgen and Wyeth Pharmaceuticals, a division of Wyeth, today announced updates to the U.S. Food and Drug Administration (FDA)-approved U.S. Prescribing Information (PI) for EnbrelÂ® (etanercept).
The U.S. PI now contains a boxed warning relating to the risk of infections, including tuberculosis, which is similar to labeling for other medicines in the tumor necrosis factor (TNF) inhibitor class. The PI had previously included a bolded warning regarding the risk of infections and tuberculosis. This information is now in a boxed warning and includes additional language regarding screening and monitoring patients for tuberculosis, including patients who tested negative for latent tuberculosis infection. In addition, the boxed warning states that tuberculosis has been observed in patients receiving TNF-blocking agents, including ENBREL, and that tuberculosis may be due to reactivation of latent tuberculosis infection or to new infection. The boxed warning notes that data from clinical trials and preclinical studies suggest that the risk of reactivation of latent tuberculosis infection is lower with ENBREL than with TNF-blocking monoclonal antibodies. The boxed warning further notes that, nonetheless, post-marketing cases of tuberculosis reactivation have been reported for TNF blockers, including ENBREL.
The risks defined in the boxed warning are consistent with the risk of tuberculosis and infections that have been included in previous versions of the U.S. PI. The primary concern of both Amgen and Wyeth is for the safety of patients, and both companies maintain an ongoing pharmacovigilance program to analyze and evaluate all safety reports from clinical and open-label trials as well as post-marketing surveillance. As always, it is important that physicians and patients fully understand the benefits and risks of ENBREL treatment.
Other PI updates include the addition of reported incidence of tuberculosis infection observed in clinical studies in the Adverse Reactions section. In global clinical studies of more than 20,000 patients, tuberculosis was observed in approximately 0.01 percent of patients. In more than 15,000 patients from clinical studies in the U.S. and Canada, tuberculosis was observed in approximately 0.007 percent of patients. The Adverse Reaction Information from Spontaneous Reports section was also updated based on post-marketing surveillance reports. Additional information was added regarding antibody assays in the immunogenicity section.
The indication within the U.S. PI for juvenile idiopathic arthritis (JIA) â€“ formerly called juvenile rheumatoid arthritis (JRA) â€“ also was changed. ENBREL now has an updated JIA indication for reducing the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older.
In addition to these U.S. PI updates, the current patient package insert (PPI) for ENBREL will be replaced with a Medication Guide when it becomes available. Patients will receive the Medication Guide when a prescription for ENBREL is dispensed in the U.S. As with the current PPI, Amgen and Wyeth will distribute the Medication Guide in conjunction with any company-sponsored patient communications about ENBREL.
Amgen and Wyeth are informing healthcare professionals about the revisions to the U.S. PI through a â€œDear Healthcare Professionalâ€ letter, and will post the letter and updated PI on www.enbrel.com. Physicians, patients and caregivers who have additional questions may contact 1-888-4ENBREL.
ENBREL is a fully human soluble tumor necrosis factor (TNF) receptor. ENBREL was first approved in 1998 for moderate to severe rheumatoid arthritis and has more than 15 years of collective clinical experience.
ENBREL indications in the U.S.:
ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with moderate to severe rheumatoid arthritis. ENBREL can be taken with methotrexate or used alone. ENBREL is indicated for reducing the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients ages 2 and older. ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with psoriatic arthritis. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone. ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis. ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Important Safety Information
What important safety information do I need to know about taking prescription ENBREL?
ENBREL is a type of protein called a tumor necrosis factor (TNF) blocker that blocks the action of a substance your body's immune system makes called TNF. People with an immune disease, such as rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis, have too much TNF in their bodies. ENBREL can reduce the amount of active TNF in the body to normal levels, helping to treat your disease. But, in doing so, ENBREL can also lower the ability of your immune system to fight infections.
Serious infections, including tuberculosis (TB), have happened in patients taking ENBREL. Some of these serious infections have been fatal. Many serious infections occurred in people prone to infection. Serious infections have also occurred in patients with advanced or poorly-controlled diabetes. Do not start Enbrel if you have an infection or are allergic to ENBREL or its components. Once on ENBREL, if you get an infection or have any sign of an infection, including fever, cough, or flu-like symptoms or have open sores on your body, tell your doctor. Your doctor should test you for TB before starting Enbrel and should monitor you closely for signs and symptoms of TB.
Serious nervous system disorders, such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes have been reported. There have been rare reports of serious blood disorders (some fatal).
In medical studies, more cases of lymphoma (a type of cancer) were seen in patients taking TNF blockers compared to similar patients who were not taking TNF blockers. The risk of lymphoma may be several-fold higher in people with rheumatoid arthritis and psoriasis; the role of TNF blockers in the development of malignancies is unknown.
Tell your doctor if you:
Think you have, are being treated for, have signs of, or are prone to infection Have any open sores Have or have had TB or hepatitis B Have ever been treated for heart failure Have ever had or develop a serious nervous system disorder Develop symptoms such as persistent fever, bruising, bleeding or paleness while taking ENBREL Common side effects in adult clinical trials were injection site reactions, infection and headache.
In a medical study of patients with JIA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults. The kinds of infections reported were generally mild and similar to those usually seen in children. Other serious adverse reactions were reported, including serious infections, depression/personality disorder.
If you have any questions about this information, be sure to discuss them with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please visit www.enbrel.com or call 1-888-4ENBREL to request additional information, including the full U.S. Prescribing Information.
About Amgen and Wyeth
Amgen and Wyeth Pharmaceuticals, a division of Wyeth, market ENBREL in North America. Wyeth markets ENBREL outside of North America. Immunex Corporation, a wholly owned subsidiary of Amgen, manufactures ENBREL.
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of womenâ€™s health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products.
Wyeth is one of the worldâ€™s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products and non-prescription medicines that improve the quality of life for people worldwide. The Companyâ€™s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health. To learn more, visit www.wyeth.com.
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Contact: Amgen, Thousand Oaks Sonia Fiorenza, 805-447-1604 (media) Arvind Sood, 805-447-1060 (investors) or Wyeth Lili Gordon, 484-865-6671 (media) Justin Victoria, 973-660-5340 (investors)