Landmark Cimzia Data in Crohn's Disease Published in New England Journal of Medicine
TORONTO, July 18, 2007 /CNW/ - Two pivotal Phase III
clinical trials demonstrating the safety and sustained
efficacy of Cimzia (certolizumab pegol) in moderate to severe
Crohn's disease (CD) have been published today in the New
England Journal of Medicine (NEJM). The PRECiSE-1 and
PRECiSE-2 studies demonstrate that a statistically
significantly greater proportion of moderate-to-severe
Crohn's disease patients achieved and sustained clinical
response with CIMZIA compared to
placebo.
CIMZIA is the first and only PEGylated anti-TNF (Tumor Necrosis
Factor) alpha antibody -- PEGylation of CIMZIA allows for
subcutaneous administration every four weeks without the need
for dose escalation. And unlike currently available anti-TNF
treatments, CIMZIA is Fc-free -- the Fc molecular region is
associated with potential in vitro cellular
cytotoxicity.
"There is an unmet need for an anti-TNF therapy with the
convenience of subcutaneous administration given every four
weeks and stable dosing for patients with moderate to severe
Crohn's disease. Based on these published results,
certolizumab pegol will be a welcome addition to our
treatment options once approved," said Dr. Brian Feagan,
Professor of Medicine, Department of Epidemiology and
Biostatistics, University of Western Ontario, Director,
London Clinical Trials Research Group, John P. Robarts
Research Institute and PRECiSE-1 investigator. "Publication
of the results from these two landmark studies in the New
England Journal of Medicine allows healthcare professionals
to better assess the effect of certolizumab pegol in the
treatment of patients with Crohn's disease. These results also
validate the PEGylated Fab' fragment concept as seen by the
outcomes of the trials."
In the two PRECiSE trials reported today, CIMZIA was
administered subcutaneously once every four weeks for 26
weeks, with induction doses at weeks 0, 2 and 4. In the
PRECiSE-1 study, patients were randomized to either CIMZIA or
placebo at the start of the study and assessed for 26 weeks.
Significantly more CIMZIA patients than those on placebo achieved
and maintained clinical response. In PRECiSE-2, patients who
responded to open-label induction therapy with CIMZIA and
subsequently remained on treatment, were more likely to have
maintained response and remission at 26 weeks than patients
who received placebo. Overall, the safety and tolerability
profile of CIMZIA was consistent with that expected of an anti-TNF
agent. The most common reported adverse events (AEs) across
both studies were headache, nasopharyngitis, cough and
abdominal pain.
Based on today's published results, CIMZIA represents a potential
future option for moderate-to-severe Crohn's disease patients
who are currently limited in their therapy options. "Broader
therapy options are always welcomed by patients such as
myself, especially in an inflammatory condition such as
Crohn's disease", says Liane Kiszczak, a Crohn's disease patient
from Edmonton, Alberta, and a CIMZIA recipient through the
PRECiSE-1 clinical trial. "As patients, the ultimate
aspiration would be eventually have a cure for Crohn's
disease. However, in the absence of a cure, effective and
convenient therapies are needed to help patients attain a high
quality of life."
Canada has been a significant contributor to the CIMZIA Crohn's
disease clinical development program, with 30 Canadian
gastroenterologist investigators and more than 260 clinical
trial patients dispersed across the country. CIMZIA has not
yet been approved by Health Canada for use in
Canada.
PRECiSE-1 Study Results(1)
The PRECiSE (PEGylated Antibody Fragment Evaluation in Crohn's
Disease) clinical trials form one of the largest, most
comprehensive development programs for an anti-TNF in Crohn's
disease, including more than 1,300 patients globally. In
PRECiSE-1, patients were randomized to either CIMZIA or
placebo at study entry without an open-label treatment induction
phase. PRECiSE-1 represents a unique trial design in Crohn's
disease - no anti-TNF has previously been evaluated in an
induction trial extending beyond 12 weeks in patients with
active Crohn's disease. In PRECiSE-1, significantly more
CIMZIA patients than those on placebo achieved and maintained
clinical response, as defined by a 100 point or greater
decrease in the Crohn's Disease Activity Index (CDAI)(2) at
Week 6 and Week 26 of the study. Specifically, 35 per cent of
CIMZIA patients versus 27 per cent of placebo patients
achieved response at Week 6 (p equals 0.02). The percentages
of patients who responded at both weeks 6 and 26 were 23 per
cent for CIMZIA versus 16 per cent for placebo (p
equals 0.02). Furthermore, significantly more CIMZIA patients
experienced improved quality of life compared to placebo at Week 26
as demonstrated by increased scores on the Inflammatory Bowel
Disease Questionnaire (IBDQ), a validated self-assessment
tool used to quantify Crohn's disease symptom
severity.(3)
In PRECiSE-1, serious adverse events (SAEs) occurred in 10.3 per
cent of CIMZIA patients, and 7.0 per cent of placebo
patients. Local injection site reactions were low (3.0 per
cent). Serious infections occurred in 2 per cent of CIMZIA
patients versus less than 1 per cent of placebo patients. Only
eight per cent of CIMZIA patients developed detectable
anti-certolizumab pegol antibodies.
PRECiSE-2 Study Results(4)
PRECiSE-2 involved an open-label induction phase during which
all patients received CIMZIA at weeks 0, 2 and 4. Responders
at Week 6 were then randomized to either CIMZIA or placebo
every four weeks (double-blind) and evaluated through Week
26. Results demonstrated 64 per cent of patients achieved
clinical response during induction, and a statistically
significant number of patients maintained response through
Week 26 on CIMZIA versus placebo. Additionally, more CIMZIA
patients achieved disease remission (defined as CDAI scores
of 150 or less) at Week 26 (48 vs. 29 per cent, p is less
than 0.001). Similar to PRECiSE-1, CIMZIA patients also
experienced improved quality of life as assessed by
IBDQ.
In PRECISE-2, serious adverse events occurred in 7 per cent of
CIMZIA patients during induction, and in 6 per cent of CIMZIA
patients versus 7 per cent of placebo patients during the
double-blind phase. Local injection reactions were low (2 per
cent during induction, and 3 per cent during the double-blind
phase on CIMZIA versus 15 per cent on placebo). Serious
infections occurred in 3 per cent of CIMZIA patients versus less
than 1 per cent of placebo patients during the double-blind
phase. Only 9 per cent of patients who entered the initial
induction phase developed detectable antibodies against
certolizumab pegol at some point during the
study.
About CIMZIA (certolizumab pegol)
CIMZIA is an investigational drug product, and is the only
Fc-free PEGylated Fab' fragment anti-TNF (Tumour Necrosis
Factor). CIMZIA is Fc-free and thus avoids potential cellular
cytotoxicity. CIMZIA has a high affinity for human TNF-alpha,
selectively neutralizing its effects. 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
autoimmune diseases.
Also, recent study results (RAPID-1 and RAPID-2) have
demonstrated CIMZIA's clinical efficacy and tolerability in
rheumatoid arthritis.(4) UCB plans to file for the treatment
of rheumatoid arthritis with regulatory agencies in the U.S.,
Europe and Canada. CIMZIA is
currently not approved for any indication in
Canada.
About UCB
Headquartered in Brussels (Belgium), UCB (http://www.ucb-group.com">www.ucb-group.com) is a leading global biopharmaceutical company dedicated to the research, development and commercialization of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology. UCB focuses on securing a leading position in severe disease categories. Employing more than 8,400 people in over 40 countries, UCB achieved revenue of 2.5 billion euro in 2006. UCB is listed on the Euronext Brussels Exchange and owns 87.6 per cent of Schwarz Pharma.
About UCB Pharma Canada
UCB Pharma Canada was officially incorporated in November, 2006 with the objective of bringing a new-generation, convenient therapy to the Canadian market for auto-immune, inflammatory diseases. A truly patient-focused organization, UCB Pharma Canada's focus is bringing new and innovative programs to patients, and the specialists who treat them, to help improve the lives of people living with severe diseases.
References
(1) Sandborn WJ et al. Certolizumab pegol for the treatment of
Crohn's disease. NEJM, 19 July
2007.
(2) The CDAI score, or Crohn's Disease Activity Index, measures the
severity of Crohn's disease by taking into account a number
of factors
such as intensity of symptoms, medication and general well-being.
Patients with higher scores have more active Crohn's disease
clinically, while
lower scores indicate the disease is less
active.
(3) The Inflammatory Bowel Disease Questionnaire (IBDQ) assesses
quality of life in patients with inflammatory bowel
diseases.
(4) Schreiber S et al. Maintenance therapy with certolizumab pegol
for Crohn's disease. NEJM, 19 July
2007.
For further information: or to schedule an interview with a local gastroenterologist, please contact Chrome Communications; Alon Barmapov, (647) 405-1352 or Tiana DiMichele, (416) 666-5331/
Posted: July 2007
