In this global, double blind, placebo-controlled, multi-center study, 583 patients were randomized to receive 50 mg of ENBREL twice weekly (n=194), 25 mg of ENBREL twice weekly (n=196) or placebo (n=193). The primary endpoint of the study was the proportion of patients achieving a 75 percent or greater improvement in the Psoriasis Area and Severity Index (also known as PASI 75) after 12 weeks of treatment. Nearly half (49 percent) of the patients treated with 50 mg of ENBREL twice weekly and more than a third (34 percent) of patients treated with 25 mg of ENBREL twice weekly achieved a PASI 75 versus 3 percent of patients receiving placebo.
"In this study, a significant number of patients experienced rapid improvement in as quickly as two weeks after receiving ENBREL," said primary investigator Dr. Kim Papp of Probity Medical Research in Waterloo, Canada. "In addition, physicians assessed their patients as having 'clear' or 'almost clear' skin in 57 percent of patients treated with ENBREL 50 mg twice weekly, and 39 percent treated with ENBREL 25 mg twice weekly, compared with 4 percent of placebo-treated patients."
Patients were asked to assess the effect of ENBREL on their psoriasis and the impact that ENBREL treatment had on their lives as measured by the Dermatology Life Quality Index over the course of the study. Patients treated with ENBREL 50 mg twice weekly reported 71 percent improvement after 12 weeks and patients treated with ENBREL 25 mg twice weekly reported 66 percent improvement. Both treatment groups experienced improvement after just two weeks of treatment.
"We have now studied ENBREL in two large and well-controlled studies of psoriasis patients," said Dr. Beth Seidenberg, Amgen's senior vice president of development. "We are encouraged by the replicated results and look forward to submitting an application to the U.S. Food and Drug Administration seeking approval for ENBREL in the treatment of a fifth inflammatory disease."
ENBREL is currently under review for a fourth inflammatory disease, ankylosing spondylitis. The supplemental application will be the subject of a U.S. Food and Drug Arthritis Advisory committee meeting on June 24, 2003.
ENBREL was generally well tolerated in the study. Adverse events were similar to those reported in previous clinical trials of ENBREL, with injection site reactions occurring more frequently than in the placebo group.
The most frequent adverse events in placebo-controlled RA clinical trials (n=349) were injection site reactions (ISR) (37%), infections (35%), and headache (17%). Only the rate of ISR was higher than that of placebo. The most frequent adverse events in a methotrexate-controlled trial (n=415) were infections (64%), ISR (34%), and headache (24%). Only the rate of ISR was higher than that of methotrexate.
Psoriasis is characterized by chronic inflammation of the skin. This inflammation drives the formation of red, itchy skin plaques that are painful and disfiguring. Tumor necrosis factor (TNF) is found at high levels in psoriatic plaques, and plays a critical role in their formation and maintenance. Psoriasis affects nearly 7 million people in the United States, one million of whom have moderate to severe plaque psoriasis.
ENBREL is not approved by the U.S. Food and Drug Administration for the treatment of psoriasis.
ABOUT ENBREL
ENBREL is the only fully human anti-TNF receptor approved for use to reduce the signs and symptoms of active arthritis in patients with psoriatic arthritis, and to reduce the signs and symptoms and inhibit the structural damage in patients with moderately to severely active rheumatoid arthritis (RA). ENBREL is the only biologic therapy approved to treat newly diagnosed RA patients, and can be used alone. It is also approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in patients as young as four years of age who have had an inadequate response to disease-modifying medicines.
Physicians have become familiar with the benefits and proven long-term tolerability profile of ENBREL. It has been used to treat over 180,000 patients worldwide since becoming commercially available four years ago.
ENBREL acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions that causes the inflammatory process. The binding of ENBREL to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, the following have been reported in patients using ENBREL:
• Serious Infections
- Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes
- Some serious infections were fatal
- Rare cases of tuberculosis
• What to do/Not do
- Do not start ENBREL if you have an infection or are allergic to ENBREL or its components
- Tell your doctor if you are prone to infection
- Stop ENBREL if a serious infection occurs
- Contact your doctor if you have questions about ENBREL or develop an infection
• Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes.
- Tell your doctor if you have ever had any of these disorders or if you develop them after starting ENBREL.
• Rare reports of serious blood disorders (some fatal)
- Contact your doctor immediately if you develop symptoms such as persistent fever, bruising, bleeding, or paleness
• The incidence of cancer has not increased with extended exposure to ENBREL and is similar to the expected rate.
• ENBREL can also cause injection site reactions.
• In a medical study of patients with JRA, 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 rarely, including serious infections (2%) and depression/personality disorder (1%)
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. Additional information about ENBREL, including full Prescribing Information, can be found on the Web site sponsored by the companies at www.enbrel.com or by calling toll free 888-4ENBREL (888-436-2735).
Amgen is a global biotechnology company that discovers, develops, manufactures and markets important human therapeutics based on advances in cellular and molecular biology.
Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, cardiovascular disease, central nervous system, inflammation, hemophilia, oncology and vaccines. Wyeth is one of the world'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 Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.
This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen's Form 10-K for the year ended December 31, 2002, and in Amgen's periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
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The statements in this press release that are not historical facts are forward-looking statements based on current expectations of future events that involve risks and uncertainties including, without limitation, risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing, and commercialization, and economic conditions, including interest and currency exchange rate fluctuations, the impact of competitive or generic products, product liability and other types of lawsuits, the impact of legislative and regulatory compliance and obtaining approvals, and patents, and other risks and uncertainties, including those detailed from time to time in Wyeth's periodic reports, including quarterly reports on Form 10-Q and the Annual Report on Form 10-K, filed with the Securities and Exchange Commission. Actual results may vary materially from the forward-looking statements. Wyeth assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
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Wyeth Pharmaceuticals
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