Abbott Seeks U.S. and E.U. Regulatory Approvals for HUMIRA(R) (Adalimumab)
as a Treatment for Juvenile Rheumatoid Arthritis
81995 & EDATE
HUMIRA Pediatric Clinical Study Demonstrated Promising Results in Juvenile
Abbott announced it has simultaneously submitted a supplemental
Application (sBLA) with the U.S. Food and Drug Administration (FDA) and a
Type II Variation to the European Medicines Agency (EMEA) seeking approval
to market HUMIRA(R) (adalimumab) as a treatment for juvenile rheumatoid
arthritis (JRA) in the U.S. and juvenile idiopathic arthritis (JIA) in the
European Union (EU). This filing marks the first pediatric indication
sought for HUMIRA.
JRA, commonly referred to as JIA in the EU, is the most common form of
arthritis in children and normally begins before the age of 16. Typical
symptoms include persistent joint pain and stiffness that are usually worse
in the morning or after a nap. The pain may limit movement of the affected
joint, although many children will not complain of the pain. Walking with a
limp is an early sign of JRA due to an affected knee. Depending on the
severity of disease, JRA may affect bone development or cause growth
abnormalities, such as one leg or arm growing longer than the other. The
goal of treatment for JRA is to control inflammation, relieve pain, and
preserve mobility and joint function, and ultimately prevent disease
" If left untreated, JRA may slow a child's growth and cause disability
into adulthood, " said J. Lovell, MD, MPH, associate director,
Special Treatment Center for Juvenile Arthritis, Cincinnati Children's
Hospital Medical Center, Cincinnati. " HUMIRA may offer hope to children
suffering with this unpredictable disease. "
About HUMIRA JRA Clinical Study
The global filing is based on the results of a Phase III, 48-week study
that included 171 children (4 to 17 years old) with polyarticular JRA, a
form of arthritis affecting five or more joints, usually the same joints on
both sides of the body. Additional data will be submitted from an ongoing
open label extension study evaluating the long-term efficacy and safety of
In the first part of the study, two groups of patients -- those taking
methotrexate (MTX) and not taking MTX -- received HUMIRA subcutaneously
every other week (EOW) for 16 weeks. Patient responses were measured using
the American College of Rheumatology (ACR) Pediatric 30 score, which
represents a 30 percent improvement in JRA signs and symptoms, such as the
number of swollen joints with loss of motion, assessment of pain and level
of disability. Children who showed a positive clinical response (n=133)
entered the second part of the study and were randomized to receive HUMIRA
or placebo for an additional 32 weeks or until disease flare. A flare was
defined as a worsening of 30 percent or more in three of the six ACR Ped
response variables, a minimum of two active joints, and no more than one
indicator improving by 30 percent.
Children receiving HUMIRA, in the second part of the study, had
significantly fewer disease flares than children on placebo, both without
MTX (43 percent vs. 71 percent) and with MTX (37 percent vs. 65 percent).
Additionally, twice as many children on HUMIRA achieved ACR Ped 70 compared
to those on placebo (56 percent vs. 28 percent, respectively) at Week 48.
The most common adverse events were infections (mostly mild upper
respiratory) and injection site reactions. No tuberculosis or opportunistic
infections were reported during this study. The adverse events observed in
children were similar to those observed in adults in previous rheumatoid
arthritis (RA) studies with HUMIRA.
HUMIRA is approved to treat adult patients with moderately to severely
active rheumatoid arthritis. More than 180,000 patients worldwide are
currently being treated with HUMIRA. HUMIRA is currently being studied in
pediatric Crohn's disease, and Abbott plans to initiate trials for
pediatric and adolescent psoriasis later this year.
" We are pleased by the submission of our first pediatric indication for
HUMIRA, " said Eugene Sun, M.D., vice president, Global Pharmaceutical
Clinical Development at Abbott. " HUMIRA has already benefited thousands of
adults suffering with RA, and this trial shows promise for children and
families who are impacted by JRA. "
Important Safety Information
Globally, prescribing information varies; refer to the individual
country product label for complete information.
Serious infections, sepsis, tuberculosis (TB) and opportunistic
infections, including fatalities, have been reported with the use of TNF-
blocking agents, including HUMIRA. Many of these serious infections have
occurred in patients also taking other immunosuppressive agents that in
addition to their underlying disease could predispose them to infections.
Infections have also been reported in patients receiving HUMIRA alone.
Treatment with HUMIRA should not be initiated in patients with active
infections. TNF-blocking agents, including HUMIRA, have been associated
with reactivation of hepatitis B (HBV) in patients who are chronic carriers
of this virus. Some cases have been fatal. Patients at risk for HBV
infections should be evaluated for prior evidence of HBV infections before
initiating HUMIRA. The combination of HUMIRA and anakinra is not
recommended and patients using HUMIRA should not receive live vaccines.
More cases of malignancies have been observed among patients receiving
TNF blockers, including HUMIRA, compared to control patients in clinical
trials. These malignancies, other than lymphoma and non-melanoma skin
cancer, were similar in type and number to what would be expected in the
general population. There was an approximately 3.5 fold higher rate of
lymphoma in combined controlled and uncontrolled open-label portions of
HUMIRA clinical trials. The potential role of TNF-blocking therapy in the
development of malignancies is not known. TNF-blocking agents, including
HUMIRA, have been associated in rare cases with demyelinating disease and
severe allergic reactions. Infrequent reports of serious blood disorders
have been reported with TNF-blocking agents.
Worsening congestive heart failure (CHF) has been observed with TNF-
blocking agents, including HUMIRA, and new onset CHF has been reported with
TNF-blocking agents. Treatment with HUMIRA may result in the formation of
autoantibodies and rarely, in development of a lupus-like syndrome.
The most frequent adverse events seen in the placebo-controlled
clinical trials in adults with rheumatoid arthritis (HUMIRA vs. placebo)
were injection site reactions (20 percent vs. 14 percent), upper
respiratory infection (17 percent vs. 13 percent), injection site pain (12
percent vs. 12 percent), headache (12 percent vs. 8 percent), rash (12
percent vs. 6 percent) and sinusitis (11 percent vs. 9 percent).
Discontinuations due to adverse events were 7 percent for HUMIRA and 4
percent for placebo. As with any treatment program, the benefits and risks
of HUMIRA should be carefully considered before initiating therapy.
In HUMIRA clinical trials for ankylosing spondylitis, psoriatic
arthritis and Crohn's disease, the safety profile for adult patients
treated with HUMIRA was similar to the safety profile seen in adult
patients with rheumatoid arthritis.
HUMIRA is the only fully human monoclonal antibody approved for the
treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and
ankylosing spondylitis (AS) in the U.S. and Europe and Crohn's disease in
the U.S. HUMIRA resembles antibodies normally found in the body. It works
by blocking tumor necrosis factor alpha (TNF-alpha), a protein that when
produced in excess, plays a central role in the inflammatory responses of
many immune- mediated diseases. Clinical trials are currently under way
evaluating the potential of HUMIRA in other autoimmune diseases.
In the U.S., HUMIRA is approved by the FDA for reducing signs and
symptoms, inducing major clinical response, inhibiting the progression of
joint structural damage, and improving physical function in adult patients
with moderately to severely active RA. HUMIRA is indicated for reducing the
signs and symptoms of active arthritis, inhibiting the progression of
structural damage and improving physical function in patients with
psoriatic arthritis. HUMIRA can be used alone or in combination with
methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs).
HUMIRA is also approved for reducing signs and symptoms in patients with
active AS. Earlier this year, HUMIRA was approved for reducing the signs
and symptoms and inducing and maintaining clinical remission in adults with
moderately to severely active Crohn's disease who have had an inadequate
response to conventional therapy, and reducing the signs and symptoms and
inducing clinical remission in these patients if they have also lost
response to or are intolerant to infliximab.
In Europe, HUMIRA, in combination with methotrexate (MTX), is indicated
for the treatment of moderate to severe, active RA in adult patients when
the response to disease-modifying anti-rheumatic drugs (DMARDs) including
MTX has been inadequate, and for the treatment of severe, active and
progressive RA in adults not previously treated with MTX. HUMIRA can be
given as monotherapy in case of intolerance to MTX or when continued
treatment with MTX is inappropriate. HUMIRA has been shown to reduce the
rate of progression of joint damage as measured by x-ray and to improve
physical function, when given in combination with MTX.
Additionally, HUMIRA is indicated for the treatment of active and
progressive PsA in adults when the response to previous DMARD-therapy has
been inadequate and for the treatment of severe, active AS in adults who
have had an inadequate response to conventional therapy.
Abbott's Commitment to Immunology
Abbott is focused on the discovery and development of innovative
treatments for immunologic diseases. The Abbott Bioresearch Center, founded
in 1989 in Worcester, Mass., United States, is a world-class discovery and
basic research facility committed to finding new treatments for immune-
In April 2007, Abbott announced the opening of Abbott Biotechnology
Limited (ABL), its new state-of-the-art biologics manufacturing facility in
Puerto Rico to support the long-term supply of HUMIRA. The new facility is
the main manufacturing site for supplying HUMIRA to patients in the U.S.
More information about HUMIRA, including full prescribing information,
is available on the Web site http://www.HUMIRA.com or in the United States
calling Abbott Medical Information at 1-800-633-9110.
Abbott is a global, broad-based health care company devoted to the
discovery, development, manufacture and marketing of pharmaceuticals and
medical products, including nutritionals, devices and diagnostics. The
company employs 65,000 people and markets its products in more than 130
Abbott's news releases and other information are available on the
company's Web site at http://www.abbott.com.