New Phase 3 ENBREL Data Show Psoriasis Patients Achieved a Therapeutic Response From 'Step Down' Dosing Regimen
THOUSAND OAKS, Calif. and COLLEGEVILLE, Pa., Feb. 7 -- A
global Phase 3 study of Enbrel(R) (etanercept) demonstrated that a significant
number of psoriasis patients given initial loading doses of ENBREL for three
months rapidly achieved psoriasis clearing and then maintained the response
while receiving half the drug dose. These data were presented at the American
Academy of Dermatology annual meeting in Washington, D.C.
In this double-blind, placebo-controlled study, 583 patients with moderate
to severe psoriasis were randomized to receive placebo (n=193), 25 mg of
ENBREL twice weekly (n=196), or a loading dose of 50 mg of ENBREL twice weekly
(n=194), for 12 weeks. Following this initial period, patients then continued
treatment for an additional 12 weeks. During the second 12 weeks, those
taking the loading dose of ENBREL were "stepped down" to half the dose (25 mg
twice weekly), while patients taking 25 mg twice weekly continued with the
same dose. Patients initially taking placebo were started on 25 mg ENBREL
twice weekly. As previously reported, patients in both groups initially
receiving ENBREL experienced improvement in psoriasis in as early as two
The new data show that during the second 12 weeks of the study, ENBREL
continued to provide significant relief of psoriasis symptoms in all groups.
Forty-nine percent of patients treated with the loading dose achieved
75 percent improvement in the Psoriasis Area Severity Index (also known as
PASI 75) in the first 12 weeks of the study as compared to 34 percent of
patients taking 25 mg twice weekly and three percent of patients taking
placebo. A large majority (77 percent) of the patients treated with the
loading dose who had achieved a PASI 75 response at week 12 maintained this
response through week 24 while receiving the stepped down dose. In addition,
at week 24, the percentage of step down patients achieving PASI 75 increased
to 54 percent.
"In this study, more step down patients achieved the clinical milestone of
PASI 75 by week 12," said Craig Leonardi, M.D., clinical associate professor
of dermatology at Saint Louis University. "It was very exciting to see that a
large majority of these patients maintained the effect while receiving half
the loading dose."
Psoriasis Patients Treated with ENBREL Stopped And Re-Started Treatment
Without Serious Side Effects From Their Psoriasis
In another presented Phase 3 study not involving step down therapy,
409 patients who had achieved at least a PASI 50 response at the conclusion of
24 weeks stopped treatment and were monitored for relapse. Patients withdrawn
from ENBREL treatment did not have serious adverse events due to psoriasis
including disease flares, hospitalizations or transformation of psoriasis to a
more severe form of the disease. After discontinuing ENBREL, the median time
to relapse (loss of half of PASI improvement achieved while on ENBREL) was
approximately three months.
After patients relapsed, they were retreated with the same dose they had
received at the end of the double-blind period of the study. Overall PASI
75 response rates at both week 12 and 24 of re-treatment (n=297 and n=174,
respectively) were similar to those seen after initial treatment in all
"Psoriasis is a chronic condition and patients must sometimes stop
treatment due to life circumstances such as pregnancy or surgery," said Alice
Gottlieb, M.D., Ph.D., director of the Clinical Research Center at University
of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.
"These data show that ENBREL was stopped and restarted without severe side
effects due to psoriasis or loss of efficacy."
ENBREL was generally well tolerated in both Phase 3 studies. Adverse
events were similar to those reported in previous clinical trials, with
injection site reactions occurring more frequently than in the placebo group.
An estimated 4.5 million people in the United States suffer from psoriasis
and 1.5 million have moderate to severe plaque psoriasis. The disease 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.
ENBREL is currently approved for the treatment of moderately to severely
active psoriatic arthritis and is currently under review by the U.S. Food and
Drug Administration for the treatment of psoriasis.
ENBREL is the only fully human TNF receptor approved to reduce signs and
symptoms, improve physical function, and inhibit the progression of structural
damage in patients with moderately to severely active rheumatoid arthritis
(RA), and to reduce the signs and symptoms and inhibit the progression of
structural damage of active arthritis in patients with psoriatic arthritis.
ENBREL is the only biologic therapy approved for first-line treatment of RA
patients, and can be used alone or in combination with methotrexate. It is
approved to reduce the signs and symptoms 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 antirheumatic
drugs (DMARDs). It is also the first biologic approved to treat the signs and
symptoms in patients with active ankylosing spondylitis (AS).
ENBREL has been used by more than 215,000 patients worldwide across
indications since becoming commercially available more than five 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 of RA, JRA,
psoriatic arthritis and AS. The binding of ENBREL to TNF renders the bound
TNF biologically inactive, resulting in significant reduction in inflammatory
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
* In medical studies of all TNF-inhibitors, a higher rate of lymphoma (a
type of cancer) was seen compared to the general population, however,
the risk of lymphoma may be up to several fold higher in RA patients.
The role of TNF-inhibitors in the development of lymphoma is unknown.
* The incidence of other cancers 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
-- 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 percent) and depression/personality
disorder (1 percent)
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.
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2002, and in Amgen's periodic reports on Form 10-Q and Form 8-K. Amgen is
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Andrea Rothschild (media)
Cary Rosansky (investors)
Douglas Petkus (media)
Justin Victoria (investors)
CONTACT: Media, Andrea Rothschild, +1-805-447-6287, or cell,
+1-818-681-8660, or Investors, Cary Rosansky, +1-805-447-1060, both of Amgen;
or media, Douglas Petkus, +1-484-865-5140, or investors, Justin Victoria,
+1-973-660-5340, both of Wyeth Pharmaceuticals/
Web site: http://www.enbrel.com
Web site: http://www.amgen.com