Centocor, Inc. announced today
that the US Food and Drug Administration (FDA) has accepted its filing of a
supplemental Biologics License Application (sBLA) for REMICADE(R)
(infliximab) for inhibiting the progression of structural damage and
improving physical function in patients with active psoriatic arthritis
(PsA). The filing is based on one-year data from the double-blind,
placebo-controlled trial IMPACT 2 and two-year data from the double-blind,
placebo-controlled trial IMPACT. PsA is a chronic, progressive and
potentially debilitating disease that causes joint inflammation and is
frequently associated with skin plaques of psoriasis.
"Findings from IMPACT 2 show that early intervention with REMICADE
therapy can significantly inhibit the progression of joint damage, which is
an important factor in the long-term prognosis of patients with psoriatic
arthritis," said Jerome A. Boscia, MD, Senior Vice President, Clinical
Research and Development, Centocor, Inc. "We are encouraged by these data
and are pleased that the FDA has accepted the file for review."
One-year radiographic analyses from IMPACT 2 showed that treatment with
REMICADE resulted in significantly greater inhibition of the progression of
structural damage, compared with placebo (as measured by the change from
baseline in van der Heijde-Sharp [vdH-S] score modified for PsA by adding
measurement for distal interphalangeal joints of the hands). In this method
a higher change in score indicates greater structural damage, while lower
change in score indicates less structural damage. At as early as 24 weeks
of treatment, REMICADE-treated patients experienced a mean change (+/-
standard deviation) in vdH-S score of -0.70 (+/- 2.53) from baseline,
compared with an average change of 0.82 (+/- 2.62) in the placebo group (P
< 0.001). At week 54, patients who received a full 54-week regimen of
REMICADE experienced a mean change of -0.94 (+/- 3.40) from baseline,
compared with an average change of 0.53 (+/- 2.60) in patients who crossed
over from placebo to REMICADE (P = 0.001) at week 16 or 24. Patients
randomized to REMICADE and placebo patients who crossed over to REMICADE
experienced a total improvement of -0.24 (+/- 2.45) and -0.29 (+/- 1.98),
respectively, from week 24 to 54, after all patients switched to treatment
with REMICADE.
REMICADE-treated patients demonstrated significant improvement in
physical function as measured by the Health Assessment Questionnaire (HAQ).
The HAQ assesses the difficulty a patient has accomplishing tasks in eight
functional areas (dressing, arising, eating, walking, hygiene, reaching,
gripping and other activities of daily living). As early as week 14,
patients in the REMICADE group experienced a median improvement of 43
percent, compared with zero percent in the placebo group (P < 0.001), and
results were maintained through one year. At week 54, there was a median 50
percent improvement in HAQ score from baseline in the group randomized to
REMICADE, and a 46 percent improvement in placebo patients who switched to
REMICADE. At week 54, 59 percent of REMICADE randomized patients and 53
percent of placebo patients who crossed over to REMICADE had improvement in
HAQ by greater than or equal to 0.3 scores, indicating clinically
meaningful improvement in physical function.
In May 2005, REMICADE was approved in the United States for reducing
signs and symptoms of active arthritis in patients with psoriatic
arthritis. In September of 2004, REMICADE received European Union (EU)
approval, in combination with methotrexate, for the treatment of active and
progressive psoriatic arthritis in patients who have responded inadequately
to disease- modifying anti-rheumatic drugs (DMARDs). Additionally, in May
2006, the Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency gave a positive opinion for the use of REMICADE
for treatment of active and progressive psoriatic arthritis in patients who
have responded inadequately to DMARDs to be used in combination with
methotrexate or alone in patients who show intolerance to methotrexate or
in whom methotrexate is contraindicated. Acceptance of the sBLA filing by
the FDA does not mean that a license has been issued for this indication
nor does it represent any evaluation of the adequacy of the data submitted
in the sBLA.
About IMPACT/IMPACT 2
The Infliximab Multinational Psoriatic Arthritis Controlled Trial
(IMPACT) was a Phase 2b, randomized, double-blind, placebo-controlled study
that involved 104 patients with active psoriatic arthritis (defined as
affecting at least five joints) who failed at least one DMARD. Patients
received either REMICADE (5 mg/kg) or placebo, administered at weeks 0, 2,
6 and 14. The REMICADE group continued on maintenance treatments every
eight weeks through week 94. Beginning at week 16, patients randomized to
the placebo group received an induction regimen of REMICADE followed by
maintenance treatment every eight weeks through week 94. Hands and feet
radiographs were taken at screening and at weeks 50 and 98. Physical
function was measured at multiple visits including screening and at weeks
16, 22, 50 and 94.
REMICADE was generally well tolerated in this study, with one REMICADE
and one placebo patient experiencing serious adverse events (AEs) in the
placebo- controlled portion of the study through week 16. Fourteen patients
out of 104 experienced serious AEs from week 16 through 50 in
placebo/REMICADE crossover and REMICADE groups together. In the second year
of IMPACT, seven patients out of 78 treated with REMICADE were reported
with serious AEs. No deaths, cases of tuberculosis or other opportunistic
infections were reported and serious infections were uncommon. There were
no serious infusion reactions. One patient had a serious AE relating to
malignancy: a ductal adenocarcinoma of the pancreas three months after week
98.
The Induction and Maintenance of Psoriatic Arthritis Clinical Trial 2
(IMPACT 2) was a Phase 3, randomized, double-blind, placebo-controlled
study of 200 patients with active psoriatic arthritis (defined as affecting
at least five joints). The study evaluated the safety and efficacy of
REMICADE in patients who had an inadequate response to DMARDs or
nonsteroidal anti- inflammatory drugs (NSAIDs). Patients received REMICADE
(5 mg/kg) at weeks 0, 2, 6 and every 8 weeks until week 46 or placebo at
weeks 0, 2, 6, 14 and 22. Placebo patients with less than 10 percent
improvement in both swollen and tender joints entered early escape and
received REMICADE at weeks 16, 18 and 22 (n=47). At week 24, placebo
patients who did not qualify for early escape received REMICADE at week 24,
26, 30, 38 and 46. Patients randomized to REMICADE who had less than 20
percent improvement in combined swollen and tender joint count received
REMICADE 10 mg/kg at weeks 38 and 46 (n=15). Patients were allowed
concomitant methotrexate use at a stable dose. Hand and foot radiographs
were taken at week 0, 24 and 54. Physical function was measured at multiple
visits including weeks 0, 14, 24 and 54.
Through 54 weeks, 12 percent of patients in combined REMICADE treatment
groups experienced serious AEs (during average follow-up of 42.8 weeks) as
compared to 6 percent of placebo patients (average follow-up 20.2 weeks).
No deaths, cases of tuberculosis or other opportunistic infections or
serious infusion reactions were reported; serious infections were uncommon.
There were two patients who were reported an AE of malignancy: one case of
basal cell carcinoma in the placebo group and one case of stage I Hodgkin
lymphoma in the REMICADE group. The only laboratory abnormalities that
occurred more frequently with REMICADE compared with placebo were asymptomatic liver
enzyme test elevations. See "Important Safety Information" below.
About Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory arthropathy manifesting
with joint pain and swelling that can lead to joint destruction and
debilitation. It is frequently associated with inflamed, scaly, red patches
of skin psoriasis. Symptoms may include stiffness and tenderness of the
joints and surrounding tissue, reduced range of motion, nail changes and
redness and pain of the eye (uveitis). Joints of the hands, wrists, knees,
ankles, feet, lower back and neck are commonly affected. Psoriasis affects
an estimated two to three percent of the world's population, and
approximately one out of three patients affected by psoriasis may develop
psoriatic arthritis. Both men and women are equally affected by psoriatic
arthritis, most commonly between the ages 30 and 50, in the peak of their
productive years.
About REMICADE
REMICADE is the global market leader among anti-tumor necrosis factor
alpha (TNF-alpha) therapies and has demonstrated broad clinical utility in
rheumatoid arthritis (RA), Crohn's disease (CD), psoriatic arthritis (PsA),
ulcerative colitis (UC), ankylosing spondylitis (AS) and pediatric Crohn's
disease (PCD). The safety and efficacy of REMICADE have been well
established in clinical trials over the past 14 years and through
commercial experience with more than 770,000 patients treated worldwide.
In the U.S., REMICADE, in combination with methotrexate, is indicated
for reducing signs and symptoms, inhibiting the progression of structural
damage and improving physical function in patients with moderately to
severely active RA. REMICADE is the only biologic indicated for reducing
signs and symptoms and inducing and maintaining clinical remission in adult
and pediatric patients with moderately to severely active CD who have had
an inadequate response to conventional therapy. REMICADE is also indicated
for reducing the number of draining enterocutaneous and rectovaginal
fistulas and maintaining fistula closure in patients with fistulizing CD.
In December 2004, REMICADE was approved for reducing signs and symptoms in
patients with active AS. In May 2005, REMICADE was approved for reducing
signs and symptoms of active arthritis in patients with PsA. Additionally,
in September 2005, REMICADE was approved for reducing signs and symptoms,
achieving clinical remission and mucosal healing, and eliminating
corticosteroid use in patients with moderately to severely active UC who
have had an inadequate response to conventional therapy. This approval
makes REMICADE the first and only biologic approved for the treatment of
moderate to severe UC. In addition, on May 19, 2006, REMICADE was approved
for reducing signs and symptoms and inducing and maintaining clinical
remission in pediatric patients with moderately to severely active Crohn's
disease who have had an inadequate response to conventional therapy. This
approval establishes REMICADE as the first and only biologic therapy
approved for the treatment of PCD.
REMICADE is unique among available anti-TNF biologic therapies. Unlike
self-administered therapies that require patients to inject themselves
frequently, REMICADE is the only anti-TNF biologic administered directly by
caregivers in the clinic or office setting. In RA (3 mg/kg), CD (5 mg/kg),
PsA (5 mg/kg), UC (5 mg/kg), and PCD (5 mg/kg), REMICADE is a two-hour
infusion administered every 8 weeks, following a standard induction regimen
that requires treatment at weeks 0, 2 and 6. As a result, REMICADE patients
may require as few as six treatments each year. In AS (5 mg/kg), REMICADE
is a two-hour infusion administered every 6 weeks, following a standard
induction regimen that requires treatment at weeks 0, 2 and 6.
Important Safety Information
Many people with heart failure should not take REMICADE; so prior to
treatment you should discuss any heart condition with your doctor. Tell
your doctor right away if you develop new or worsening symptoms of heart
failure (such as shortness of breath or swelling of your ankles or feet).
There are reports of serious infections, including tuberculosis (TB),
sepsis and pneumonia. Some of these infections have been fatal. Tell your
doctor if you have had recent or past exposure to people with TB. Your
doctor will evaluate you for TB and perform a skin test. If you have latent
(inactive) TB, your doctor should begin TB treatment before you start
REMICADE. REMICADE can lower your ability to fight infections, so if you
are prone to or have a history of infections, or develop any signs of an
infection such as fever, fatigue, cough, or the flu while taking REMICADE,
tell your doctor right away. Also tell your doctor if you have lived in a
region where histoplasmosis or coccidioidomycosis is common.
Reports of a type of blood cancer called lymphoma in patients on
REMICADE or other TNF blockers are rare but occur more often than expected
for people in general. People who have been treated for rheumatoid
arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis
for a long time, particularly those with highly active disease may be more
prone to develop lymphoma. Cancers, other than lymphoma, have also been
reported. Children and young adults who have been treated for Crohn's
disease with REMICADE have developed a rare type of lymphoma that often
results in death. These patients also were receiving drugs known as
azathioprine or 6-mercaptopurine. If you take REMICADE or other TNF
blockers, your risk for developing lymphoma or other cancers may increase.
You should also tell your doctor if you have had or develop lymphoma or
other cancers or if you have a lung disease called chronic obstructive
pulmonary disease (COPD).
There have been rare cases of serious liver injury in people taking
REMICADE, some fatal. Contact your doctor immediately if you develop
symptoms such as jaundice (yellow skin and eyes), dark brown urine,
right-sided abdominal pain, fever, or severe fatigue.
Blood disorders have been reported, some fatal. Tell your doctor if you
develop possible signs of blood disorders such as persistent fever,
bruising, bleeding, or paleness while taking REMICADE. Nervous system
disorders have also been reported. Tell your doctor if you have or have had
a disease that affects the nervous system, or if you experience any
numbness, weakness, tingling, or visual disturbances while taking REMICADE.
Serious infusion reactions have been reported with REMICADE, including
hives, difficulty breathing, and low blood pressure. Reactions have
occurred during or after infusions. In clinical studies, some people
experienced the following common side effects: respiratory infections (that
may include sinus infections and sore throat), coughing, and stomach pain
or mild reactions to infusion such as rash or itchy skin.
Please read important information about REMICADE, including full US
prescribing information, at remicade.
About Centocor
Centocor is harnessing the power of world-leading research and
biomanufacturing to deliver innovative biomedicines that transform
patients' lives. Centocor has already brought innovation to the treatment
of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic
arthritis, ulcerative colitis and pediatric Crohn's disease.
The world leader in monoclonal antibody production and technology,
Centocor has brought critical biologic therapies to patients suffering from
debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary
of Johnson & Johnson.
Centocor, Inc.
remicade
View drug information on Remicade.
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