New Data Presented From WELCOME Trial Show Positive Impact of Cimzia (certolizumab pegol) on Hospitalizations and Surgeries in Patients With Prior Infliximab Failure
No statistical difference observed between two studied dosing regimens
SAN DIEGO, Oct. 26 /PRNewswire/ -- According to new results from
the WELCOME trial, exploratory data analyzing the impact of
treatment with CIMZIA® (certolizumab pegol) - the only
PEGylated anti-TNF (alpha) (Tumor Necrosis Factor alpha) -
administered either every two weeks or every four weeks, showed
that the majority of Crohn's disease patients in both dosing groups
experienced no hospitalizations and surgical procedures during the
course of the 26-week study. These exploratory data from the
WELCOME trial, which studied patients who had been on the anti-TNF
therapy infliximab, but failed or developed a hypersensitivity to
the treatment, will be presented this week at the American College
of Gastroenterology (ACG) Annual Meeting.
CIMZIA is indicated for reducing the signs and symptoms of
Crohn's disease and maintaining clinical response in adult patients
with moderately to severely active disease who have had an
inadequate response to conventional therapy. The recommended
initial adult dose of CIMZIA is 400mg at Weeks 0, 2 and 4. In
patients who obtain a clinical response, the recommended
maintenance regimen is 400 mg every four weeks.
In the WELCOME trial, which evaluated moderate to severe Crohn's
disease patients who were intolerant to or no longer responding to
infliximab therapy, more than 60 percent (329 out of 539 patients
enrolled) responded to a 6-week, open label, induction phase with
CIMZIA (400 mg subcutaneously at weeks 0, 2, and 4). Patients were
then randomized at week 6 to receive CIMZIA (400 mg) every two
(q2w) or four (q4w) weeks until week 26 in a double-blind,
maintenance comparison phase. Responders were defined as those with
a decrease in CDAI score greater than or equal to 100 points from
baseline at week 6. The number and length of hospitalizations,
number of emergency room visits, and number of medical procedures
were recorded during the WELCOME study. The post-hoc analysis of
the WELCOME trial evaluated CIMZIA's impact on the incidence of
hospitalization and surgical procedures during hospital stays. The
majority of patients (86 percent) in both groups (n=139 out of 161
in the q2w group; n=145 out of 168 in the q4w group) underwent no
hospitalizations, with ten percent in the q2w group (n=16 out of
161) and nine percent in the q4w group (n=15 out of 168) requiring
one hospital stay. (Abstract #P678)
"The data suggest that the recommended 400mg q4w dosing works as
well as the accelerated dosing interval in this refractory
population, adding to the extensive results from the WELCOME
trial," said study investigator Douglas Wolf, M.D., Atlanta
Gastroenterology Associates, Atlanta, Ga. "Treatment with CIMZIA
may impact the number of hospital visits and related surgeries
based on these findings."
There were no statistically significant differences in the mean
number of hospital stays (0.193 vs. 0.208; p=0.964), duration of
the hospital stay (1.398 vs. 1.679; p=0.986) and surgical
procedures performed during hospital stays (0.037 vs. 0.030;
p=0.950) between the two CIMZIA treatment groups, as measured by
the Wilcoxon signed-rank test.
Additional data from the WELCOME study presented at ACG includes: -- Improvement in work productivity and daily activities by certolizumab pegol in Crohn's disease patients with prior loss of response or intolerance to infliximab (Abstract #P679) -- Efficacy of certolizumab pegol in Crohn's disease patients with secondary failure to infliximab is not affected by concomitant medications (Abstract #P701) -- Regain of response and remission by dose adjustment in patients with Crohn's disease who responded to certolizumab pegol: results from the WELCOME study (Abstract #P699) -- Efficacy of certolizumab pegol is not affected by baseline anti-infliximab antibody status in patients with Crohn's disease with secondary infliximab failure (Abstract #P702)
"Crohn's is highly individualized and these data provide
additional insight into how use of CIMZIA may impact the need for
hospitalization or surgery while treating this complicated
disease," said David Robinson, vice president and general manager
of UCB's Immunology Business Unit.
In previously reported data from the WELCOME study, CIMZIA
demonstrated a low incidence of injection site pain, in less than
2% of cases. Common adverse events (AEs) included: headache;
nasopharyngitis, or the common cold; nausea; vomiting; pyrexia, or
fever; and arthralgia, or joint pain. Serious adverse events (SAEs)
were present in 7% of cases, and were most commonly
gastrointestinal (5%) or infections and infestations (2%).
Earlier this year, UCB announced that CIMZIA is available to
adult moderate to severe Crohn's patients in a pre-filled syringe,
developed in partnership with OXO Good Grips® for subcutaneous
self-administration once every four weeks after initial dosing.
CIMZIA, manufactured by UCB, was approved by the U.S. Food and Drug
Administration on April 22, 2008 for reducing signs and symptoms of
moderate to severe Crohn's disease and maintaining clinical
response in adult patients who have had an inadequate response to
conventional therapy.
About WELCOME
The WELCOME study is a 539 patient Phase IIIb multicenter
26-Week trial Evaluating the clinical benefit and tolerability of
certoLizumab pegol induCtiOn and Maintenance in patients suffering
from Crohn's disease with prior loss of response or intolErance to
infliximab. It consists of an open-label induction phase (400 mg of
CIMZIA subcutaneously at Weeks 0, 2 and 4) and a double-blind
maintenance period (400 mg of CIMZIA every 2 or 4 weeks from Week
6). The primary endpoint was defined as the rate of response
(defined as a decrease in CDAI score >=100 points from baseline)
at Week 6. Remission was defined as a CDAI score of <=150
points. The secondary endpoints are to assess and compare the
clinical efficacy of CIMZIA 400 mg maintenance therapy administered
q4w or q2w over 26 weeks; to assess the clinical efficacy of CIMZIA
400 mg as induction and two regimens of maintenance therapy on
patient reported outcome scores; to evaluate tolerability and
safety of CIMZIA; and to evaluate the effect of certolizumab pegol
induction and maintenance therapy on plasma CRP levels.
About Crohn's Disease
Crohn's disease is a chronic, progressive, destructive disorder
that causes inflammation of the gastrointestinal (GI) tract, most
commonly at the end of the small intestine (the ileum) and
beginning of the large intestine (the colon). The inflammation may
be caused by the presence of high levels of Tumor Necrosis Factor
(TNF) found in people with Crohn's disease. If not effectively
treated, it may result in the need for surgery and hospitalization.
Crohn's disease has been estimated to affect as many as half a
million Americans. People with Crohn's can experience an ongoing
cycle of flare-up and remission throughout their lives. Together
with ulcerative colitis, Crohn's disease is an inflammatory bowel
disease (IBD).
About CIMZIA® (certolizumab pegol)
CIMZIA is the only PEGylated anti-TNF (Tumor Necrosis Factor).
CIMZIA has a high affinity for human TNF-alpha, selectively
neutralising the pathophysiological effects of TNF-alpha. Over the
past decade, TNF-alpha has emerged as a major target of basic
research and clinical investigation. This cytokine plays a key role
in mediating pathological inflammation, and excess TNF-alpha
production has been directly implicated in a wide variety of
immunological diseases. The U.S. Food and Drug Administration (FDA)
has approved CIMZIA for reducing signs and symptoms of Crohn's
disease and maintaining clinical response in adult patients with
moderate to severe active disease who have had an inadequate
response to conventional therapy and for the treatment of adults
with moderately to severely active rheumatoid arthritis (RA).
CIMZIA was approved in Switzerland for induction of a clinical
response and for the maintenance of a clinical response and
remission in patients with active Crohn's disease who have not
responded adequately to conventional treatment in September 2007.
Health Canada and the European Commission have both approved CIMZIA
in combination with methotrexate (MTX), for the treatment of
moderate to severe active RA in adult patients inadequately
responsive to disease-modifying antirheumatic drugs (DMARDs)
including MTX. UCB is also developing CIMZIA in other autoimmune
disease indications. CIMZIA is a registered trademark of UCB PHARMA
S.A.
IMPORTANT SAFETY INFORMATION Risk of Serious Infections
Patients treated with CIMZIA are at an increased risk for
developing serious infections that may lead to hospitalization or
death. Most patients who developed these infections were taking
concomitant immunosuppressants such as methotrexate or
corticosteroids. CIMZIA should be discontinued if a patient
develops a serious infection or sepsis. Reported infections
include:
-- Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before CIMZIA use and during therapy. Treatment for latent infection should be initiated prior to CIMZIA use. -- Invasive fungal infections, including histoplasmosis , coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness . -- Bacterial, viral and other infections due to opportunistic pathogens.
The risks and benefits of treatment with CIMZIA should be
carefully considered prior to initiating therapy in patients with
chronic or recurrent infection. Patients should be closely
monitored for the development of signs and symptoms of infection
during and after treatment with CIMZIA, including the possible
development of tuberculosis in patients who tested negative for
latent tuberculosis infection prior to initiating therapy.
Serious and sometimes fatal infection due to bacterial,
mycobacterial, invasive fungal, viral or other opportunistic
pathogens has been reported in patients receiving TNF-blocking
agents. Among opportunistic infections, tuberculosis,
histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis,
listeriosis, and pneumocystosis were the most common. Treatment
with CIMZIA should not be initiated in patients with an active
infection, including clinically important localized infections.
CIMZIA should be discontinued if a patient develops a serious
infection or sepsis. Patients who develop a new infection during
treatment with CIMZIA should be closely monitored, undergo a prompt
and complete diagnostic workup appropriate for immunocompromised
patients, and appropriate antimicrobial therapy should be
initiated. Appropriate empiric antifungal therapy should also be
considered while a diagnostic workup is performed for patients who
develop a serious systemic illness and reside or travel in regions
where mycoses are endemic.
Malignancies
During controlled and open-labeled portions of CIMZIA studies of
Crohn's disease and other diseases , malignancies (excluding
non-melanoma skin cancer) were observed at a rate of 0.5 per 100
patient-years among 4,650 CIMZIA-treated patients versus a rate of
0.6 per 100 patient-years among 1,319 placebo-treated patients. In
studies of CIMZIA for Crohn's disease and other investigational
uses, there was one case of lymphoma among 2,657 CIMZIA-treated
patients and one case of Hodgkin lymphoma among 1,319
placebo-treated patients. In CIMZIA RA clinical trials
(placebo-controlled and open label) a total of three cases of
lymphoma were observed among 2,367 patients. This is approximately
2-fold higher than expected in the general population. Patients
with RA, particularly those with highly active disease, are at a
higher risk for the development of lymphoma. The potential role of
TNF blocker therapy in the development of malignancies is not
known.
Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset
CHF have been reported with TNF blockers. CIMZIA has not been
formally studied in patients with CHF. Exercise caution when using
CIMZIA in patients who have heart failure and monitor them
carefully.
Hypersensitivity
Symptoms compatible with hypersensitivity reactions, including
angioedema, dyspnea, hypotension, rash, serum sickness, and
urticaria, have been reported rarely following CIMZIA
administration. If such reactions occur, discontinue further
administration of CIMZIA and institute appropriate therapy.
Hepatitis B Reactivation
Use of TNF blockers, including CIMZIA, may increase the risk of
reactivation of hepatitis B virus (HBV) in patients who are chronic
carriers of this virus. Some cases have been fatal. Evaluate
patients at risk for HBV infection for prior evidence of HBV
infection before initiating CIMZIA therapy. Exercise caution in
prescribing CIMZIA for patients identified as carriers of HBV, with
careful evaluation and monitoring prior to and during treatment. In
patients who develop HBV reactivation, discontinue CIMZIA and
initiate effective anti-viral therapy with appropriate supportive
treatment.
Neurologic Reactions
Use of TNF blockers, including CIMZIA, has been associated with
rare cases of new onset or exacerbation of clinical symptoms and/or
radiographic evidence of demyelinating disease. Rare cases of
neurological disorders, including seizure disorder, optic neuritis,
and peripheral neuropathy have been reported in patients treated
with CIMZIA. Exercise caution in considering the use of CIMZIA in
patients with these disorders.
Hematologic Reactions
Rare reports of pancytopenia, including aplastic anemia, have
been reported with TNF blockers. Medically significant cytopenia
(e.g., leukopenia, pancytopenia, thrombocytopenia) has been
infrequently reported with CIMZIA. Advise all patients to seek
immediate medical attention if they develop signs and symptoms
suggestive of blood dyscrasias or infection (e.g., persistent
fever, bruising, bleeding, pallor) while on CIMZIA. Consider
discontinuation of CIMZIA therapy in patients with confirmed
significant hematologic abnormalities.
Drug Interactions
An increased risk of serious infections has been seen in
clinical trials of other TNF blocking agents used in combination
with anakinra or abatacept. Formal drug interaction studies have
not been performed with rituximab or natalizumab; however because
of the nature of the adverse events seen with these combinations
with TNF blocker therapy, similar toxicities may also result from
the use of CIMZIA in these combinations. Therefore, the combination
of CIMZIA with anakinra, abatcept, rituximab, or natalizumab is not
recommended. Interference with certain coagulation assays has been
detected in patients treated with CIMZIA. There is no evidence that
CIMZIA therapy has an effect on in vivo coagulation. CIMZIA may
cause erroneously elevated aPTT assay results in patients without
coagulation abnormalities.
Autoimmunity
Treatment with CIMZIA may result in the formation of
autoantibodies and, rarely, in the development of a lupus-like
syndrome. Discontinue treatment if symptoms of lupus-like syndrome
develop.
Immunizations
Do not administer live vaccines or attenuated vaccines
concurrently with CIMZIA.
Adverse Reactions
In controlled Crohn's clinical trials, the most common adverse
events that occurred in >=5% of CIMZIA patients (n=620) and more
frequently than with placebo (n=614) were upper respiratory
infection (20% CIMZIA, 13% placebo), urinary tract infection (7%
CIMZIA, 6% placebo), and arthralgia (6% CIMZIA, 4% placebo). The
proportion of patients who discontinued treatment due to adverse
reactions in the controlled clinical studies was 8% for CIMZIA and
7% for placebo.
In controlled RA clinical trials, the most common adverse events
that occurred in >= 3% of patients taking CIMZIA 200 mg every
other week with concomitant methotrexate (n=640) and more
frequently than with placebo with concomitant methotrexate (n=324)
were upper respiratory tract infection (6% CIMZIA, 2% placebo),
headache (5% CIMZIA, 4% placebo), hypertension (5% CIMZIA, 2%
placebo), nasopharyngitis (5% CIMZIA, 1% placebo), back pain (4%
CIMZIA, 1% placebo), pyrexia (3% CIMZIA, 2% placebo), pharyngitis
(3% CIMZIA, 1% placebo), rash (3% CIMZIA, 1% placebo), acute
bronchitis (3% CIMZIA,1% placebo), fatigue (3% CIMZIA, 1% placebo).
Hypertensive adverse reactions were observed more frequently in
patients receiving CIMZIA than in controls. These adverse reactions
occurred more frequently among patients with a baseline history of
hypertension and among patients receiving concomitant
corticosteroids and non-steroidal anti-inflammatory drugs. Patients
receiving CIMZIA 400mg as monotherapy every 4 weeks in RA
controlled clinical trials had similar adverse reactions to those
patients receiving CIMZIA 200mg every other week. The proportion of
patients who discontinued treatment due to adverse reactions in the
controlled clinical studies was 5% for CIMZIA and 2.5% for
placebo.
Please visit http://cimzia.com/crohns-disease/pdf/Prescribing_Information.pdf
for full prescribing information.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical
company dedicated to the research, development and
commercialization of innovative medicines with a focus on the
fields of central nervous system and immunology disorders.
Employing approximately 10 000 people in over 40 countries, UCB
generated revenue of EUR 3.6 billion in 2008. UCB is listed on
Euronext Brussels (symbol: UCB).
Forward-Looking Statement
This press release contains forward-looking statements based on
current plans, estimates and beliefs of management. Such statements
are subject to risks and uncertainties that may cause actual
results to be materially different from those that may be implied
by such forward-looking statements contained in this press release.
Important factors that could result in such differences include:
changes in general economic, business and competitive conditions,
effects of future judicial decisions, changes in regulation,
exchange rate fluctuations and hiring and retention of its
employees.
Source: UCB
CONTACT: Bert Kelly, Manager, U.S. Communications & Public
Relations,
UCB Group, M: +1-404-784-6303, Bert.Kelly@ucb.com; or Tanya Jishi,
Biosector
2, M: +1-917-216-9619, tjishi@biosector2.com
Web Site: http://www.ucb.com/
Posted: October 2009