New Efficacy Data Shows Cimzia (certolizumab pegol) Provides Long-Term Remission of Moderate to Severe Crohn's Disease Regardless of Prior Anti-TNF Exposure, According to Data Presented at DDW
- Oral presentation highlights sustained Crohn's Disease remission data over four years - regardless of prior treatment with anti-TNF agents - Results provide new information about treatment strategies for patients with active Crohn's Disease who have previously responded to Cimzia® (certolizumab pegol)
ATLANTA, May 2 /PRNewswire/ -- UCB announced today results of an
open-label extension study, PRECiSE 4 (P4), of Cimzia®
(certolizumab pegol; CZP) demonstrating that Cimzia provides
sustained efficacy over four years in moderate to severe Crohn's
Disease patients regardless of whether patients were previously
treated with infliximab (IFX) or infliximab-naive.
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.
P4 is a long-term open label continuation of the Phase III
PRECiSE 2 (P2) subpopulation assessing the long-term efficacy,
safety and tolerability of CZP patients. P4 was open to patients
from the CZP or placebo arm of P2. Patients from the treatment arm
of P2 received an additional 400mg dose at week 2 and continued
400mg every four weeks thereafter. Patients from the placebo arm
received 400mg doses at weeks 0, 2 and 4 and every 4 weeks
thereafter.
Disease remission was measured using the Harvey-Bradshaw Index
at 1, 2, 3 and 4 years among all patients, and, separately, a
subset of 84 patients with no previous IFX exposure. These data
support the use of Cimzia long term in moderate to severe Crohn's
Disease patients.
Remission rates, calculated using observed case (OC) analyses
were as follows:
Year 1 Year 2 Year 3 Year 4
All patients 62.7% 70.0% 63.3% 57.7%
(42/67) (32/46) (19/30) (15/26)
IFX-naive
patients 68.0% 71.4% 60.0% 62.5%
(34/50) (25/35) (12/20) (10/16)
Remission rates over four years were comparable among CD
patients previously enrolled in the P2 Phase III study in patients
previously treated with IFX and IFX-naive patients.
Additionally, these P4 data demonstrate that patients who are
losing response to Cimzia can be recaptured with one additional
dose of Cimzia at week 2 during their regular four week dosing
regimen. These data were presented today by Dr. William Sandborn,
Vice-Chair, Department of Gastroenterology and Hepatology, Mayo
Clinic, as an oral presentation at Digestive Disease Week (DDW)
2010 in New Orleans.
"These data are important to gastroenterologists treating
Crohn's Disease as it can be a complex disease to manage," said Cem
Kayhan, M.D., associate medical director, UCB. "It is important
that there is a simple recapture strategy for patients who may be
flaring, regardless of their prior infliximab experience."
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). 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.
About Cimzia
Certolizumab pegol is the only PEGylated anti-TNF (Tumor
Necrosis Factor). It has a high affinity for human TNF-alpha,
selectively neutralizing 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 diseases. The U.S. Food and Drug Administration (FDA) has
approved certolizumab pegol 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. It is also approved for the
treatment of adults with moderately to severely active rheumatoid
arthritis. Certolizumab pegol 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.
Please visit www.cimzia.com for full prescribing information for CIMZIA®. IMPORTANT SAFETY INFORMATION Risk of Serious Infections and Malignancy
Patients treated with certolizumab pegol 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. Certolizumab Pegol 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 certolizumab pegol use and during therapy.
Treatment for latent infection should be initiated prior to
certolizumab pegol 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 certolizumab pegol
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 certolizumab pegol,
including the possible development of tuberculosis in patients who
tested negative for latent tuberculosis infection prior to
initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported
in children and adolescent patients treated with TNF blockers, of
which certolizumab pegol is a member. Certolizumab pegol is not
indicated for use in pediatric patients.
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 certolizumab pegol should not be initiated in patients with an
active infection, including clinically important localized
infections. Certolizumab pegol should be discontinued if a patient
develops a serious infection or sepsis. Patients who develop a new
infection during treatment with certolizumab pegol 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 certolizumab
pegol 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 certolizumab pegol-treated
patients versus a rate of 0.6 per 100 patient-years among 1,319
placebo-treated patients. In studies of certolizumab pegol for
Crohn's Disease and other investigational uses, there was one case
of lymphoma among 2,657 certolizumab pegol-treated patients and one
case of Hodgkin lymphoma among 1,319 placebo-treated patients. In
certolizumab pegol 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.
Malignancies, some fatal, have been reported among children,
adolescents, and young adults who received treatment with
TNF-blocking agents (initiation of therapy less than or equal to 18
years of age), of which certolizumab pegol is a member.
Approximately half of the cases were lymphoma (including Hodgkin's
and non-Hodgkin's lymphoma), while the other cases represented a
variety of different malignancies and included rare malignancies
associated with immunosuppression and malignancies not usually
observed in children and adolescents. Most of the patients were
receiving concomitant immunosuppressants.
Cases of acute and chronic leukemia have been reported with
TNF-blocker use. Even in the absence of TNF-blocker therapy,
patients with RA may be at a higher risk (approximately 2-fold)
than the general population for developing leukemia.
Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset
CHF have been reported with TNF blockers. Certolizumab pegol has
not been formally studied in patients with CHF. Exercise caution
when using certolizumab pegol 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 certolizumab pegol
administration. If such reactions occur, discontinue further
administration of certolizumab pegol and institute appropriate
therapy.
Hepatitis B Reactivation
Use of TNF blockers, including certolizumab pegol, 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 certolizumab pegol therapy.
Exercise caution in prescribing certolizumab pegol for patients
identified as carriers of HBV, with careful evaluation and
monitoring prior to and during treatment. In patients who develop
HBV reactivation, discontinue certolizumab pegol and initiate
effective anti-viral therapy with appropriate supportive
treatment.
Neurologic Reactions
Use of TNF blockers, including certolizumab pegol, 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 certolizumab pegol. Exercise caution in
considering the use of certolizumab pegol 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 certolizumab pegol. 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 certolizumab
pegol. Consider discontinuation of certolizumab pegol 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 certolizumab pegol in these combinations. Therefore, the
combination of certolizumab pegol with anakinra, abatacept,
rituximab, or natalizumab is not recommended. Interference with
certain coagulation assays has been detected in patients treated
with certolizumab pegol. There is no evidence that certolizumab
pegol therapy has an effect on in vivo coagulation. Certolizumab
pegol may cause erroneously elevated aPTT assay results in patients
without coagulation abnormalities.
Autoimmunity
Treatment with certolizumab pegol 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 certolizumab pegol.
Adverse Reactions
In controlled Crohn's clinical trials, the most common adverse
events that occurred in greater than or equal to 5% of certolizumab
Pegol patients (n=620) and more frequently than with placebo
(n=614) were upper respiratory infection (20% certolizumab pegol,
13% placebo), urinary tract infection (7% certolizumab pegol, 6%
placebo), and arthralgia (6% certolizumab pegol, 4% placebo). The
proportion of patients who discontinued treatment due to adverse
reactions in the controlled clinical studies was 8% for
certolizumab pegol and 7% for placebo.
In controlled RA clinical trials, the most common adverse events
that occurred in greater than or equal to 3% of patients taking
certolizumab pegol 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% certolizumab pegol, 2% placebo), headache (5%
certolizumab pegol, 4% placebo), hypertension (5% certolizumab
pegol, 2% placebo), nasopharyngitis (5% certolizumab pegol, 1%
placebo), back pain (4% certolizumab pegol, 1% placebo), pyrexia
(3% certolizumab pegol, 2% placebo), pharyngitis (3% certolizumab
pegol, 1% placebo), rash (3% certolizumab pegol, 1% placebo), acute
bronchitis (3% certolizumab pegol,1% placebo), fatigue (3%
certolizumab pegol, 1% placebo). Hypertensive adverse reactions
were observed more frequently in patients receiving certolizumab
pegol than in controls. These adverse reactions occurred more
frequently among patients with a baseline history of hypertension
and among patients receiving concomitant corticosteroids and
nonsteroidal anti-inflammatory drugs. Patients receiving
certolizumab pegol 400mg as monotherapy every 4 weeks in RA
controlled clinical trials had similar adverse reactions to those
patients receiving certolizumab pegol 200mg every other week. The
proportion of patients who discontinued treatment due to adverse
reactions in the controlled clinical studies was 5% for
certolizumab pegol and 2.5% for placebo.
Please see full prescribing information at www.cimzia.com before
prescribing.
For further Information: Bert Kelly, Communications and Public Relations Manager, UCB 404.784.6303, Bert.Kelly@ucb.com Rich Ferreira, Cooney/Waters Group 212.886.2202, rferreira@cooneywaters.com 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 more than 9,000 people in over 40 countries, UCB produced
revenue of EUR 3.1 billion in 2009. 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, Communications and Public Relations
Manager, UCB,
+1-404-784-6303, Bert.Kelly@ucb.com, Rich Ferreira,
Cooney/Waters Group,
+1-212-886-2202, rferreira@cooneywaters.com
Web Site: http://www.cimzia.com/
http://www.ucb.com/
Posted: May 2010
