Study of ENBREL and Methotrexate Shows Two-Thirds of Patients Reduce
Methotrexate Use by 63% on Average; One-Third Completely Discontinue
Methotrexate
SEATTLE, June 15 /PRNewswire/ -- In clinical data presented this week from
three long-term studies of moderately to severely active rheumatoid arthritis
(RA) patients receiving ENBREL(R) (etanercept), a sustained therapeutic
response was demonstrated with no significant increase in the type or rate of
side effects over time. The data, some of which represent the longest study
to date of patients on a therapy to inhibit tumor necrosis factor (TNF) in RA,
are being presented this week at the European League Against Rheumatism
(EULAR) meeting in Prague.
"These studies show that many patients using ENBREL experience symptomatic
improvement, not only within two weeks of starting ENBREL, but can sustain
that improvement when measured over the long-term," says Leslie Garrison,
Senior Vice President, Clinical Development at Immunex Corporation
(Nasdaq: IMNX).
ENBREL is the only TNF inhibitor approved for use without methotrexate, a
drug that has been the most commonly used disease modifying drug for RA.
ENBREL is indicated for reducing signs and symptoms and inhibiting structural
damage in patients with moderately to severely active rheumatoid arthritis.
The first study is open-label and includes adult patients who had failed
other DMARDs (disease modifying anti-rheumatic agents) and are using ENBREL as
monotherapy. The patients had been enrolled in previous studies of ENBREL:
71 patients were studied for more than four years; 358 patients were studied
for more than three years; 430 patients were studied for more than two years
and 479 patients were studied for more than one year. The following four year
data were presented by Larry Moreland, MD, of the University of
Alabama-Birmingham:
-- 24% of patients had zero swollen joints
-- 28% of patients had zero tender joints
-- 21% of patients had disability scores of zero
-- 74% of patients achieved the ACR 20
-- 49% of patients achieved an ACR 50
-- 26% of patient achieved an ACR 70
-- More than half of patients decreased their steroid use by 72% on
average
-- 32% of patients have completely discontinued steroid use
ENBREL was generally well tolerated over the four years of this study. In
the study, no significant differences in the type or rate of adverse events
were seen in patients treated with ENBREL over time. Serious adverse events
occurred at a rate of 0.14 per patient-year in the long-term study compared to
0.13 in the patients treated with ENBREL and 0.20 in placebo patients in the
previous controlled studies. Likewise, serious infection (associated with
hospitalization or IV antibiotics) occurred at a rate of 0.04 per patient year
in the long-term study, compared to 0.04 per patient year in patients treated
with ENBREL and 0.05 in placebo patient in the controlled studies. The number
of malignancies reported in patients treated with ENBREL was similar to
expected numbers calculated from the National Cancer Institute SEER database
(12 reported vs. 15 expected). No opportunistic infections have been observed
in patients treated with ENBREL in the long-term study.
Study of ENBREL and Methotrexate Shows Two-Thirds Of Patients Reduce
Methotrexate Use By 62% On Average
A presentation by Roy M. Fleishmann, MD, of Metroplex Clinical Research
Center in Dallas TX, demonstrated that in a combination study of ENBREL and
methotrexate that followed patients (who had failed other DMARDS) for three
years, patients' symptoms improved significantly while methotrexate use was
reduced.
"Enbrel is effective, generally well tolerated, and can enable many
patients to reduce, eliminate, or avoid the use of methotrexate," says Scott
W. Baumgartner, MD of Spokane, WA. "This is valuable, because some patients
are unable or do not wish to use methotrexate due to side effect or
tolerability issues."
Sixty-seven of 79 patients remain on the long-term, open-label study. Of
these, 76 were studied for at least one year, 63 for at least two years, and
41 for at least three years. At the start of the study all patients were
taking approximately 18 mg of methotrexate per week, but had persistent
symptoms. At three years:
-- 68% of patients have reduced their methotrexate dose by 62% on average
-- 29% of patients were able to completely discontinue methotrexate use
-- 42% of patients were able to completely discontinue steroid use
-- 78% of patients achieved an ACR 20
-- 49% of patients achieved an ACR 50
-- 29% of patients achieved an ACR 70
No significant differences have been seen in the type and rate of adverse
events observed over time, when compared to the earlier controlled study of
ENBREL plus methotrexate.
ENBREL Shown Effective as First-Line Therapy in Two -Year Study
In a third study, presented by Mark Genovese, MD from Stanford University,
632 patients who had been newly diagnosed (within three years) with RA
received either ENBREL or methotrexate in a double-blind, randomized,
placebo-controlled trial. Patients on the study had not previously received
DMARDS, including methotrexate. The study, which demonstrates long-term
efficacy and tolerability for ENBREL, includes the following results for the
ENBREL (25 mg dose) and methotrexate (20 mg on average) treatment groups after
two years:
-- 72% of patients using ENBREL achieved an ACR 20 compared to 59% of
patients receiving methotrexate
-- 70% of patients using ENBREL experienced no new joint erosions at two
years, compared to 58% of patients receiving methotrexate
Statistically different side effects between patients in this study
treated with ENBREL and methotrexate (seen in greater than 10% of patients)
were:
-- 35% of patients using ENBREL experienced mild to moderate injection
site reactions
-- 31% of patients using methotrexate experienced nausea
-- 17% of patients using methotrexate experienced mouth ulcers
-- 12% of patients using methotrexate experienced hair loss
Two percent of patients experienced methotrexate lung toxicity. The rate
of infections was 1.39 events per patient year for patients using ENBREL,
compared to 1.70 events per patient year for patients receiving methotrexate.
There were no opportunistic infections. Serious infections were infrequent in
both treatment groups.
ABOUT ENBREL
An application for marketing approval of ENBREL was fast-tracked by the
U.S. Food and Drug Administration in 1998. Six months after the application
was submitted, the FDA approved ENBREL for reducing the signs and symptoms of
moderately to severely active RA in patients who have had an inadequate
response to one or more DMARDs. The following year, the FDA approved ENBREL
for reducing signs and symptoms of moderately to severely active
polyarticular-course juvenile rheumatoid arthritis in patients who have had an
inadequate response to DMARDs. In June 2000, the FDA approved ENBREL for
reducing signs and symptoms and inhibiting structural damage in patients with
moderately to severely active RA as part of an sBLA. ENBREL is the only TNF
inhibitor that can be used both alone or with methotrexate. It is also the
only TNF inhibitor approved to be used as a first-line therapy.
ENBREL acts by binding TNF, one of the dominant cytokines or proteins that
play an important role in normal immune function and the cascade of reactions
that cause the inflammatory process of RA. ENBREL competitively inhibits
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.
Since the product was first introduced, serious infections, some involving
death, have been reported in patients using ENBREL. Many of these infections
occurred in patients who were prone to infections, such as those with advanced
or poorly controlled diabetes. Rare cases of tuberculosis have also been
reported. ENBREL should be discontinued in patients with serious infections.
Do not start ENBREL if you have an infection of any type or if you have an
allergy to ENBREL or its components. ENBREL should be used with caution in
patients prone to infection. Contact your physician if you have any questions
about ENBREL or infections.
There have been rare reports of 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. There have also been rare reports of serious blood
disorders, some involving death. Contact your doctor immediately if you
develop symptoms such as persistent fever, bruising, bleeding, or paleness.
It is unclear if ENBREL has caused these nervous system or blood disorders. If
your doctor confirms serious blood problems, you may need to stop using
ENBREL.
The most frequent adverse events in placebo-controlled clinical trials
involving 349 adults 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
clinical trial of 415 adults with early-stage RA were infections (64%), ISR
(34%), and headache (24%). Only the rate of ISR was higher than that of
methotrexate. In all 1,197 RA patients studied, malignancies were rare (1%).
In a study of 69 patients with JRA, infections (62%), headache (19%),
abdominal pain (19%), vomiting (13%), and nausea (9%)occurred more frequently
than in adults. The types of infections reported in JRA patients were
generally mild and consistent with those commonly seen in children. Serious
adverse reactions reported rarely were chicken pox (3%), gastroenteritis (3%),
depression/personality disorder (1%), skin ulcer (1%), inflammation in parts
of the upper digestive tract (1%), group A streptococcal septic shock (1%),
type I diabetes mellitus (1%), and soft tissue and post-operative wound
infection (1% each).
Immunex Corporation and Wyeth-Ayerst Laboratories market ENBREL in North
America. Other AHP affiliates market ENBREL outside of North America.
Immunex manufactures ENBREL. Additional information about ENBREL, including
full prescribing information, can be found on the company-sponsored Web site
at (http://www.enbrel.com) or by calling toll-free 888-4ENBREL (888-436-2735).
Immunex Corporation is a leading biopharmaceutical company dedicated to
improving lives through immune system science innovations.
American Home Products Corporation's Wyeth-Ayerst division 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, oncology and hemophilia products
and generic pharmaceuticals.
American Home Products Corporation 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 also is a global
leader in vaccines, biotechnology and animal health care.
NOTE: Except for the historical information contained herein, this news
release contains forward-looking statements that involve substantial risks and
uncertainties. Among the factors that could cause actual results or timelines
to differ materially are risks associated with research and clinical
development, regulatory approvals, our supply capabilities and reliance on
third-party manufacturers, product commercialization, competition, litigation
and other risk factors listed from time to time in reports filed by Immunex
with the SEC, including but not limited to risks described under the caption
"Important Factors That May Affect Our Business, Our Results of Operations and
Our Stock Price" within our most recently filed Form 10-Q. The
forward-looking statements contained in this news release represent our
judgment as of the date of this release. Immunex undertakes no obligation to
publicly update any forward-looking statements. An electronic version of this
news release -- as well as additional information about Immunex of interest to
investors, customers, future employees and patients -- is available on the
Immunex home page at http://www.immunex.com.
SOURCE Immunex Corporation
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CONTACT:
media, Robin Shapiro, 206-389-4040, or
investors, Mark Leahy, 206-389-4363, both of Immunex; or Doug
Petkus of Wyeth-Ayerst, 610-902-7336
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