Pivotal Cimzia Data in Crohn's Disease Published in New EnglandJournal of Medicine
-- First PEGylated anti-TNF Highlighted in Two Articles -- -- Data Confirm CIMZIA(TM) Efficacy in Treatment of Crohn's Disease --
Brussels, Belgium/Atlanta, GA -- Wednesday, July 18, 2007, 11 p.m. CET/5 p.m. ET -- Two pivotal Phase III clinical trials demonstrating the safety and sustained efficacy of CIMZIA(TM) (certolizumab pegol) in moderate-to-severe Crohn's disease (CD) were published in two articles in the July 19 issue of 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(TM) compared to placebo. CIMZIA(TM) was administered subcutaneously every four weeks to 26 weeks, with induction doses at weeks 0, 2 and 4. Patients who responded to open-label induction therapy with CIMZIA(TM), and subsequently remained on treatment, were more likely to have maintained response and remission at 26 weeks than patients who received placebo in the PRECiSE 2 trial.
CIMZIA(TM) is an investigational agent for the treatment of Crohn's disease and represents the first and only PEGylated anti-TNF (Tumor Necrosis Factor) alpha antibody. PEGylation of CIMZIA(TM) allows for subcutaneous administration every four weeks without evident need for dose escalation. Unlike currently available treatments, CIMZIA(TM) is Fc-free. The Fc region is associated with potential in vitro cellular cytotoxicity.
Lead investigators of the studies were William J. Sandborn, M.D., Professor of Medicine at the Mayo Clinic College of Medicine, Rochester, Minnesota, USA (PRECiSE 1) and Professor Stefan Schreiber, Hospital for General Internal Medicine, University-Hospital Schleswig-Holstein, Christian Albrechts University, Kiel, Germany (PRECiSE 2).
"There is an unmet need for an anti-TNF therapy with the convenience of subcutaneous administration 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," said Professor Schreiber. "Publication of the results from these two large multinational studies by the New England Journal of Medicine allows healthcare professionals to collectively assess the effect of the PEGylated anti-TNF certolizumab pegol in the treatment of patients with Crohn's disease."
In PRECiSE 1, patients were randomized to either CIMZIA(TM) 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(TM) patients 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 percent of CIMZIA(TM) patients versus 27 percent of placebo patients achieved response at Week 6 (p= 0.02). The percentages of patients who responded at both weeks 6 and 26 were 23 percent for CIMZIA(TM) versus 16 percent for placebo (p= 0.02). Furthermore, significantly more CIMZIA(TM) 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)
PRECiSE 2 Study Results(4)
PRECiSE 2 involved an open-label induction phase during which all patients received CIMZIA(TM) at weeks 0, 2 and 4. Responders at Week 6 were then randomized to either CIMZIA(TM) or placebo every four weeks (double-blind) and evaluated through Week 26. Results demonstrated 64 percent of patients achieved clinical response during induction, and a statistically significant number of patients maintained response through Week 26 on CIMZIA(TM) versus placebo irrespective of baseline C-reactive protein (CRP) levels (63 vs. 36 percent, p< 0.001). Additionally, more CIMZIA(TM) patients achieved disease remission (defined as CDAI scores of 150 or less) at Week 26 (48 vs. 29 percent, p< 0.001). Similar to PRECiSE 1, CIMZIA(TM) patients also experienced improved quality of life as assessed by IBDQ.
The safety and tolerability profile of CIMZIA(TM) was consistent with that expected of an anti-TNF agent. The most common reported AEs across both studies were headache, nasopharyngitis, cough and abdominal pain.
In PRECiSE 1, serious adverse events (SAEs) occurred in 10.3 percent of CIMZIA(TM) patients, and 7.0 percent of placebo patients. Local injection reactions were low (3.0 percent). Serious infections occurred in 2 percent of CIMZIA(TM) patients versus less than 1 percent of placebo patients. Only eight percent of CIMZIA(TM) patients developed detectable anti-certolizumab pegol antibodies.
In PRECiSE 2, SAEs occurred in 7 percent of CIMZIA(TM) patients during induction, and in 6 percent of CIMZIA(TM) patients versus 7 percent of placebo patients during the double blind phase. Local injection reactions were low (2 percent during induction, and 3 percent during the double-blind phase on CIMZIA(TM) versus 15 percent on placebo). Serious infections occurred in 3 percent of CIMZIA(TM) patients versus less than 1 percent of placebo patients during the double-blind phase. Only 9 percent of patients who entered the initial induction phase developed detectable antibodies against certolizumab pegol at some point during the study.
PRECiSE Clinical Trials Program
The PRECiSE clinical trials (PEGylated Antibody Fragment Evaluation in Crohn's Disease), sponsored by UCB, form the basis for regulatory submissions to U.S. and European regulatory authorities for CIMZIA(TM). The globally- conducted PRECiSE program, composed of two placebo-controlled studies and two open-label safety follow-up studies, is one of the largest, most comprehensive development programs for an anti-TNF in Crohn's disease, including more than 1,300 patients.
In addition to the PRECiSE 1 and 2 studies, PRECiSE 3 and 4 are long term, open label trials assessing the longer-term safety and tolerability of CIMZIA(TM) up to five years. Interim PRECiSE 3 data, recently presented at Digestive Disease Week 2007, demonstrated that CIMZIA(TM) maintained long- term response, up to 18 months, at stable doses in those patients responding to CIMZIA(TM) in PRECiSE 2.
About CIMZIA(TM) (certolizumab pegol)
CIMZIA(TM) is an investigational drug product. CIMZIA(TM) is the only PEGylated anti-TNF (Tumor Necrosis Factor). CIMZIA(TM) is Fc-free and thus avoids potential cellular cytotoxicity. 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.
UCB filed a Biologics Licensing Agreement (BLA) with the Food and Drug Administration (FDA) for CIMZIA(TM) in the treatment of Crohn's disease on February 28, 2006 and on April 28, 2006 submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) for the same indication.
Recent study results (RAPID 1 and RAPID 2) have demonstrated CIMZIA(TM)'s clinical efficacy and tolerability in rheumatoid arthritis.(5,6) Preparation for a regulatory submission for CIMZIA(TM) in the treatment of RA is ongoing, with filing planned in the U.S. and Europe by the end of 2007.
About Crohn's Disease
Crohn's disease is a chronic disorder that causes inflammation of the gastrointestinal (GI) tract, most commonly at the end of the small intestine (the ileum) and in the large intestine (the colon). People with Crohn's disease may suffer all of their lives, experiencing an ongoing cycle of "flare-up" and remission. Together with ulcerative colitis, Crohn's disease is an inflammatory bowel disease (IBD).(7)
Headquartered in Brussels (Belgium), UCB 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% of Schwarz Pharma. U.S. Headquarters are located in Atlanta, Georgia.
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.
5. Keystone E et al. The anti-TNF certolizumab pegol in combination with methotrexate is significantly more effective than methotrexate alone in the treatment of patients with active rheumatoid arthritis: Preliminary results from the RAPID 1 study. Presented at EULAR, 2007.
6. Smolen J et al. Efficacy and safety of certolizumab pegol in combination with methotrexate in patients with active rheumatoid arthritis despite methotrexate therapy: Results from the RAPID 2 study. Presented at EULAR, 2007.
7. Crohn's and Colitis Foundation of America. Disease Information page.
Posted: July 2007