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Cimzia Maintains Remission in Crohn's Disease New Analysis of PRECiSE 2 Study Revealed at DDW

LOS ANGELES, C.A. -- May 31, 2006 -- UCB announced today results from a new analysis of the pivotal PRECiSE 2 study, demonstrating significantly more Crohn's disease (CD) patients maintained clinical remission when treated with Cimzia™ (certolizumab pegol, CDP870) compared to patients treated with placebo at six months.

The results were presented today at Digestive Disease Week 2006 (DDW). Results from PRECiSE 2 showed that 60.6% of patients who achieved disease remission during the four-week induction treatment with Cimzia, also remained in remission at six months while receiving once-monthly, subcutaneously administered Cimzia.

"Most physicians who treat Crohn's disease make treatment decisions based on how patients are responding at each clinical visit," said Professor Stefan Schreiber, Professor of Medicine and Gastroenterology at the Christian-Albrechts University, Kiel, Germany, and principal investigator in the PRECiSE 2 study.

"Remission is obviously the endpoint that really counts in daily practice as it describes an almost complete resolution of symptoms. It is much harder to achieve than response, which is just a decrease in the disease activity score. Our results, which showed that a large portion of Cimzia patients maintain clinical remission, therefore reflect a more clinically relevant method for analyzing these kinds of trials and provide data that practicing physicians can use in making treatment decisions. The stable once-monthly subcutaneous administration after induction represents a welcomed convenience benefit for patients and healthcare professionals."

UCB recently submitted licensing requests for Cimzia to the U.S. and European regulatory authorities. When approved, Cimzia would be the first-ever biologic allowing subcutaneous injections and the first and only PEGylated Fab' fragment of a humanized anti-TNF-alpha antibody for the treatment of Crohn's disease.

Study Design and Results
The PRECiSE 2 clinical study treated moderate to severe Crohn's disease patients with open-label induction Cimzia therapy administered subcutaneously at Weeks 0, 2, and 4.

Patients responding to treatment (64.1%; based on achieving a >/=100 point drop in Crohn's Disease Activity Index (CDAI)) were then randomized at Week 6 to either monthly placebo or Cimzia treatment and followed for a total of 26 weeks.

Upon randomization, 42% of responders had achieved remission on Cimzia, defined as a CDAI score of ≤150. At Week 26, 60.6% of Cimzia patients maintained their clinical remission status, compared to only 34.2% of placebo patients (P <.001). Moreover, the median CDAI score at Week 26 remained below the 150 remission criterion in the Cimzia group, while the placebo group score did not (148.0 versus 195.4, P <.001). Additionally, in this trial 62.8% of Cimzia patients, compared to 36.2% of placebo patients (P <.001), maintained their overall clinical response (i.e., >/=100 point drop in CDAI score) at Week 26.

In PRECiSE 2, serious adverse events occurred in 5.6% of Cimzia patients during the double blind phase. One case of tuberculosis, which responded well to anti-tuberculosis therapy, was observed in the Cimzia arm of the PRECiSE 2 trial.

Local injection reactions were low in PRECiSE 2 (2.8%), and less frequent than seen with placebo. The percentage of patients who tested positive for auto-antibody formation at Week 26 (and were negative at baseline) was only 8.3% for anti-nuclear antibodies and 1.0% for anti-double-stranded DNA antibodies in PRECiSE 2. No cases of lupus were reported.

Data from the PRECiSE 1 trial, presented at DDW for the first time, further reinforce the ability of Cimzia to maintain clinical remission at week 26. The percentage of patients who achieved remission four weeks after randomization to either Cimzia or placebo was 19.5% versus 11.3% (P <.01). At 26 weeks post-randomization, the percentages were 29.5% for the Cimzia group versus 18.3% for the placebo group (P <.05). At week 6 alone and at weeks 6 and 26 combined, the remission trends were in favor of Cimzia, but did not reach statistical significance (21.6% versus 17.2% at week 6, and 14.4% versus 9.8% at weeks 6 and 26 combined, Cimzia versus placebo respectively).

"These robust results were observed using a rigorous clinical design in which all eligible Crohn's disease patients were randomized to either Cimzia or placebo at study baseline without pre-selecting responders from an unblinded treatment induction period and then treated for 26 weeks. The results seen in treatment with stable monthly subcutaneous dosing of Cimzia are equivalent to those expected in a potent anti-TNF," commented PRECiSE 1 lead investigator Dr. William J. Sandborn, Professor of Medicine at the Mayo Clinic College of Medicine.

About Cimzia
Cimzia is the first and only PEGylated Fab' fragment of a humanized anti-TNF-alpha antibody (TNF; Tumor Necrosis Factor). The engineered Fab' fragment retains the biologic potency of the original antibody. Cimzia 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 the PRECiSE Program
The PRECiSE program is the largest, most comprehensive development program for an anti-TNF in Crohn's disease. The PRECiSE clinical program is composed of four studies (PRECiSE 1, 2, 3, and 4).
· PRECiSE 1 is the most robust statistical design for regulatory demonstration of efficacy
· PRECiSE 2 is the largest study to date demonstrating efficacy in a clinically-relevant design
· PRECiSE 3 offers long-term follow-up of patients completing PRECiSE 1 and 2
· PRECiSE 4 offers open-label follow-up of patients withdrawing from PRECiSE 1 and PRECiSE 2 due to disease deterioration
· In combination, the PRECiSE program enrolled and demonstrated efficacy in the most diverse patient population for an anti-TNF in Crohn's disease, including those with prior experience with anti-TNF agents.

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 diarrhea, abdominal pain, and loss of appetite/weight, fever or rectal bleeding. 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.


REFERENCES:
1. The CDAI score, or Crohn's Disease Activity Index, measures the severity of Crohn's disease by taking into account a number of actors 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.
2.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.
3. Crohn's and Colitis Foundation of America. Disease Information page: http://www.ccfa.org/info/about/crohns Accessed April 7, 2006.


SOURCE: UCB

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