Healthcare Industry News: Inflammatory Bowel Disease
News Release - May 22, 2006
New CIMZIA (TM) Data from PRECiSE Program Reinforce Robust Efficacy in Once-Monthly Treatment of Crohn's Disease and Consistent Tolerability ProfileUnique, placebo-controlled trial demonstrates statistically significant results without pre-selecting responders
BRUSSELS, BELGIUM--(Healthcare Sales & Marketing Network)--May 22, 2006 -- Brussels, Belgium - May 22, 2006 - New pivotal Phase III trial (PRECiSE 1) data presented today at Digestive Disease Week 2006 (DDW) in Los Angeles have demonstrated that when compared with placebo, a significantly greater proportion of moderate to severe Crohn's disease patients achieved clinical response with subcutaneous once-monthly CIMZIA(TM) (certolizumab pegol, CDP870), a new type of anti-Tumor Necrosis Factor (anti-TNF) therapy.
The results from PRECiSE 1 demonstrating clinical effectiveness and tolerability are significant because they come from the most robust and rigorous placebo-controlled clinical trial design conducted to date with anti-TNFs in Crohn's disease and reinforce those seen in previous CIMZIA(TM) trials. PRECiSE 1 is the first reported Phase III trial of an anti-TNF in Crohn's disease, extending beyond four weeks, in which eligible patients were randomized at study baseline without pre-selection of responders. The overall PRECiSE clinical trial program anchored the recent UCB regulatory submission packages in both the United States and Europe and represent the largest and broadest patient clinical trial database for any biological treatment for Crohn's disease.
"The PRECiSE 1 results indicate that CIMZIA(TM), administered subcutaneously with a simple and stable once-monthly dose following an induction phase requiring only one additional administration at week 2, was a highly potent and effective therapy for patients with moderate to severe Crohn's disease," said Dr. William J. Sandborn, Professor of Medicine at the Mayo Clinic College of Medicine, USA, and lead investigator for the PRECiSE 1 clinical trial. "These significant results were demonstrated using a demanding design in which, for the first time, all eligible Crohn's disease patients were randomized to either CIMZIA(TM) or placebo at study baseline without pre-selecting responders from an unblinded treatment induction period and treated for a period longer than four weeks."
Results from PRECiSE 1 confirmed that both co-primary endpoints were met with statistical significance, and demonstrate that compared to placebo a statistically greater percentage of CIMZIA(TM) patients achieved a clinical response, defined as at least a 100-point reduction in Crohn's Disease Activity Index (CDAI) scores.[i] Overall, more CIMZIA(TM) patients achieved clinical response than placebo patients at Weeks 4, 6, 26 and weeks 6 and 26 combined: Week 4: 28.7% CIMZIA(TM) versus 21.8% placebo [p < 0.05]; Week 6: 35.2% CIMZIA(TM) versus 26.8% placebo [p < 0.05]; Week 26: 37.2% CIMZIA(TM) versus 26.6% placebo [p < 0.05]; Weeks 6 and 26: 23.1% CIMZIA(TM) versus 16.0% placebo [p < 0.05]. These data refer to response in the overall intention-to-treat (ITT) population.
Additionally, the percentage of patients who experienced remission (defined as achieving CDAI scores of < =150) at week 4 and separately at week 26 was statistically significant with CIMZIA(TM) (Week 4: 19.5% CIMZIA(TM) vs. 11.3% placebo [p < 0.01]; Week 26: 29.5% CIMZIA(TM) vs. 18.3% placebo [p < 0.05]).
The PRECiSE 1 trial included more than 650 adult patients with moderate to severe Crohn's disease. Patients were randomized to receive placebo or subcutaneous CIMZIA(TM) 400 mg at Weeks 0, 2, 4, and every four weeks thereafter through Week 24.
"PRECiSE 1 results shared at DDW 2006 reflect similar efficacy when compared to the strong PRECiSE 2 results previously presented," said Olav Hellebo, President of Inflammation Operations for UCB. "In fact, when looking at different anti-TNF studies, we found that the overall remission rate at 26 weeks is a key indicator of treatment success. The six month remission rates - 30% for PRECiSE 1 and 31% for PRECiSE 2 as well as the open-label response of 64.1% observed in PRECiSE 2 at week 6 - are highly encouraging to us in the development of CIMZIA(TM) as a potential new therapy in Crohn's disease."[ii]
Tolerability and Safety Data from PRECiSE 1 and 2
Data presented at DDW 2006 also included a combined analysis of tolerability and safety data from the PRECiSE 1 and 2 clinical trials representing a combined set of more than 1,300 Crohn's disease patients.
Professor Stefan Schreiber, Professor of Medicine and Gastroenterology at the Christian-Albrechts University, Kiel, Germany, and lead author of the combined safety abstract commented on the results. "The combined analysis suggests that CIMZIA(TM) is well-tolerated with consistent results in more than 1,300 patients. The observed low incidence of autoimmune-antibody formation may also be of interest to the clinician. The low rate of injection site reactions also underscores its potential value for the patients."
Data from the double-blind phases of both trials demonstrated that CIMZIA(TM) was generally well tolerated. The most common CIMZIA(TM) adverse events reported included headache, nasopharyngitis, infections, abdominal pain, and cough. In PRECiSE 1, serious adverse events (SAEs) occurred in 10.3% of CIMZIA(TM) patients, and 7.0% of placebo patients. In PRECiSE 2, a similar number of CIMZIA(TM) (5.6%) and placebo (6.6%) patients reported SAEs occurring during the double-blind phase. Local injection reactions were low across both studies (in PRECiSE 1, 2.7% and in PRECiSE 2, 2.8%), and less frequent than seen with placebo.
The incidence of patients who tested positive for auto-antibody formation at Week 26 (and were negative at baseline) was only 1.8% in PRECiSE 1 and 8.3% in PRECiSE 2 for anti-nuclear antibodies, and only 1.4% in PRECiSE 1 and 1.0% in PRECiSE 2 for anti-double-stranded DNA antibodies.
"The combined clinical study experience is extensive with CIMZIA(TM)," said Dr. Sandborn. "Physicians and patients can be confident that CIMZIA(TM) is well-studied, efficacious, and well-tolerated. Pending approval, CIMZIA(TM) will be a welcome addition to the treatment options for Crohn's disease."
PRECiSE Clinical Trials Program - Largest and Broadest Trial Database
The PRECiSE Program, composed of four studies (PRECiSE 1, 2, 3, and 4), is the largest, most comprehensive development program for an anti-TNF in Crohn's disease, including over 1,300 patients.
PRECiSE 1 is a unique, ground-breaking trial in Crohn's disease - a phase III trial of this nature (a 26-week, double-blind, placebo-controlled study without an induction phase to pre-select responders and re-randomization) has not been attempted previously.
In the previously reported PRECiSE 2 study, patients responding to open-label induction therapy with CIMZIA(TM) were randomized to either placebo or CIMZIA(TM) and followed for a total of 26 weeks.[ii] In this trial, 62.8% of CIMZIA(TM) patients, compared to 36.2% of placebo patients, maintained clinical response at Week 26 (p < 0.001). Similarly, 47.9% of CIMZIA(TM) patients were in clinical remission compared to 28.6% on placebo (p < 0.001).
PRECiSE 3 and 4 are both long-term open-label trials assessing the longer-term safety and tolerability of CIMZIA(TM) and are currently ongoing.
CIMZIA(TM) is the first and only PEGylated Fab' fragment of a humanized anti-TNF-alpha antibody (TNF; Tumour Necrosis Factor). The engineered Fab' fragment retains the biologic potency of the original antibody. CIMZIA(TM) 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.
About Crohn's Disease
Crohn's disease is a chronic and debilitating inflammatory disease of the gastrointestinal tract, most commonly affecting the end of the small intestine (the ileum) and beginning of the large intestine (the colon). Together with ulcerative colitis, Crohn's disease belongs to the group of illnesses known as Inflammatory Bowel Disease. Crohn's disease affects nearly one million people worldwide including an estimated 500,000 people in the United States. People with Crohn's disease may suffer an ongoing cycle of "flare-up" and remission. Symptoms of the disease include persistent diarrhoea, abdominal pain, and loss of appetite/weight, fever or rectal bleeding.[iii] In an effort to provide Crohn's disease patients with disease management information and resources designed expressly with their needs in mind, UCB has launched CrohnsAndMe.com - a dynamic, cutting-edge web site focused on helping patients thoroughly understand Crohn's disease and live with it every day.
UCB (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 8,500 people in 40 countries, UCB achieved revenues of EUR 2.3 billion in 2005. UCB is listed on the Euronext Brussels Exchange with a market capitalization of approximately EUR 6.0 billion. Worldwide headquarters are located in Brussels, Belgium.
DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 20-25, 2006, at the Los Angeles Convention Center. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit www.ddw.org.
This news release contains forward-looking statements that involve risks and uncertainties, including statements with respect to the safety, efficacy and potential benefits of certolizumab pegol, the development and commercialization of certolizumab pegol. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: the results of research, development and clinical trials; the timing and success of submission, acceptance, and approval of regulatory filings; the time and resources UCB devotes to the development and commercialization of certolizumab pegol and the scope of UCB's patents and the patents of others. In addition, the statements in this press release represent UCB's expectations and beliefs as of the date of this press release. UCB anticipates that subsequent events and developments may cause these expectations and beliefs to change. However, while UCB may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing UCB's expectations or beliefs as of any date subsequent to the date of this press release.
[i] 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 high scores have highly active Crohn's disease, while low scores indicate the disease is less active.
[ii] Schreiber et al. Certolizumab pegol, a humanised anti-TNF PEGylated Fab' fragment is safe and effective in the maintenance of response and remission following induction in active Crohn's disease: a Phase III study (PRECiSE). Gut 2005; 54 (Suppl VII) A82.
[iii] Source: Crohn's and Colitis Foundation of America. Disease Information page: http://www.ccfa.org/info/about/crohns Accessed April 7, 2006.
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