Approval of ENBREL in Patients With Early Rheumatoid Arthritis Recommended
By FDA Advisory Committee
GAITHERSBURG, Md., April 11 /PRNewswire/ -- The U.S. Food and Drug
Administration's Arthritis Advisory Committee today unanimously recommended
approval of ENBREL(R) (etanercept) for use to delay radiographic progression
of joint damage in patients with early rheumatoid arthritis (RA), and voted in
favor of approval of ENBREL for use to improve signs and symptoms of patients
with early stage disease.
The panel's recommendations today were based on data presented by
officials of Immunex (Nasdaq: IMNX), the bulk of which were the radiographic
and clinical results of a phase III randomized, double-blind, multi-center
trial that included 632 adults who had RA for less than three years and had
never been treated previously with methotrexate.
The 632 participants in the ENBREL "ERA" study were randomized to receive
either 25 mg or 10 mg of ENBREL, or up to 20 mg of methotrexate per week for
12 months. To ensure blinding of study treatments, patients received both
injections and pills: ENBREL by injections twice weekly plus placebo pills
weekly or methotrexate pills weekly plus placebo injections twice weekly.
Patients enrolled in this study had RA for a relatively short time (mean of
1 year), and had very active disease (mean tender and swollen joint counts of
30 and 24, respectively, and reported a mean duration of four hours of morning
stiffness). All patients had risk factors for rapidly progressive, erosive RA
including the presence of rheumatoid factor and or erosions on baseline x-rays
of the hands, wrists and feet.
The ability of ENBREL and methotrexate to delay joint damage
characteristic of RA was assessed using radiographic (x-ray) criteria,
measured by the modified total Sharp scoring method, a validated method used
in clinical trials to quantify progression or lack thereof, of joint
destruction. Radiographs of the hands/wrists and feet of each patient were
obtained at baseline and at 6 and 12 months. Digitized images of each
radiograph were scored by 2 of 6 physicians (five radiologists and one
rheumatologist) who were trained in the modified total Sharp scoring method.
The assessors were blinded to study treatment and the chronological order of
the images.
The modified total Sharp scoring method required seventeen joints of each
hand/wrist and six joints of each forefoot to be scored for erosions on a
scale from zero (no damage) to five. Sixteen joints of each hand/wrist and
5 joints of each forefoot were also scored for joint space narrowing on a
scale of zero (no damage) to four. The erosion score and the narrowing score
were added to determine the total Sharp Score (TSS).
The co-primary endpoint of the study was the effect on markers of activity
of RA as measured by the ACR-N AUC, which uses the American College of
Rheumatology standard composite scoring method including: assessment of
71 joints for tenderness and 68 joints for swelling; a physician's and
patient's global assessment of disease; a patient's assessment of pain, using
a visual analog scale; a patient's assessment of disability (Health Assessment
Questionnaire); and blood serum levels of ESR and CRP. Each patient is
assigned an actual percent improvement from baseline on these criteria on each
visit (the ACR-N). The ACR-N AUC represents the average amount of improvement
over all of the visits for each patient. The mean ACR-N AUC for the patients
in each group is used to compare the groups.
ABOUT ENBREL
The FDA approved ENBREL on November 2, 1998 to treat moderately to
severely active rheumatoid arthritis in patients who have an inadequate
response to one or more disease-modifying anti-rheumatic drugs (DMARDs). The
FDA included children and teen-agers (age 4-17 years) in the ENBREL label when
it granted the drug a new indication on May 28, 1999 for the treatment of
moderately to severely active polyarticular-course juvenile rheumatoid
arthritis patients who have had an inadequate response to one or more DMARDs.
IN POSTMARKETING USE, SERIOUS INFECTIONS AND SEPSIS, INCLUDING FATALITIES,
HAVE BEEN REPORTED. MANY OF THESE EVENTS OCCURRED IN PATIENTS PREDISPOSED TO
INFECTIONS, SUCH AS THOSE WITH ADVANCED OR POORLY CONTROLLED DIABETES.
DISCONTINUE ENBREL IN PATIENTS WITH SERIOUS INFECTIONS OR SEPSIS. DO NOT
START ENBREL IN THE PRESENCE OF SEPSIS, INFECTION (INCLUDING CHRONIC OR
LOCALIZED), OR ALLERGY TO ENBREL OR ITS COMPONENTS. USE CAUTION IN PATIENTS
PREDISPOSED TO INFECTION. The most frequent adverse events in adult clinical
trials in rheumatoid arthritis (n=349) were injection site reactions (ISR)
37%, infections (35%) and headache (17%). Malignancies were rare (<1%). Only
the rate of ISR was higher than placebo.
In a JRA study (n=69), 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 outpatient pediatric populations.
Serious adverse reactions reported rarely were varicella (3%), gastroenteritis
(3%), depression/personality disorder (1%), cutaneous ulcer (1%), and
esophagitis/gastritis (1%).
The first in a new class of rheumatoid arthritis (RA) drugs known as
biologic response modifiers, ENBREL is an entirely new approach to the
management of rheumatoid arthritis. 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
(TNFR) sites. The binding of ENBREL to TNF renders the bound TNF biologically
inactive, resulting in significant reduction in inflammatory activity.
Immunex Corporation and Wyeth-Ayerst Laboratories, division of American
Home Products Corporation (NYSE: AHP), 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 website at (http://www.enbrel.com) or by
calling toll-free 888-4ENBREL (888-436-2735).
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.
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 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.
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 filed by Immunex, including the
most recently filed 10-K and 10-Q. For more information, please refer to
http://www.immunex.com.
SOURCE Immunex Corporation
 back to top
Related links:
http://www.immunex.com
Company News On-Call:
http://www.prnewswire.com/comp/434644.html or fax,
800-758-5804, ext. 434644
CONTACT:
Tim Warner of Immunex Corp., 206-470-4193; or
Doug Petkus of Wyeth-Ayerst, 610-971-4980, for Immunex Corp.
|
