anybody remember how large the Centocor trial was?
Tuesday July 30, 7:31 am Eastern Time
Press Release
SOURCE: Celltech Group plc
Celltech Announces Results From CDP 571 Phase III Studies in Crohn's Disease
SLOUGH, England, July 30 /PRNewswire-FirstCall/ -- Celltech Group plc (NYSE: CLL; London: CCH) today announced outline results from a Phase III study undertaken to evaluate CDP 571 as a new treatment for active Crohn's disease, and also from a further Phase III study in steroid-dependent Crohn's disease patients.
The principal study, involving 400 patients, assessed the efficacy and safety of CDP 571 in achieving acute clinical responses, and in maintaining responses over 28 weeks. CDP 571 was administered intravenously, at 8-weekly intervals, at a dose of 10mg/kg. Treatment-related benefit was assessed by the numbers attaining a significant reduction in Crohn's disease activity index (CDAI) or disease remission.
CDP 571 treatment achieved statistically significant efficacy in respect of a range of acute and 28-week clinical endpoints, which are summarized below. The 28-week combined primary endpoint (CDAI reduction > or = 100 points and/or remission) was not reached when analyzed on an intent to treat (ITT) basis, but did achieve statistical significance on per protocol data analysis. Importantly, the product displayed an excellent safety profile, with very low immunogenicity observed on repeated dosing.
Celltech has also conducted a pilot open label study in patients who are hypersensitive to infliximab, which demonstrated that CDP 571 is well tolerated in these patients. CDP 571 also demonstrated encouraging efficacy in relation to acute endpoints in this study.
Celltech plans to seek guidance from US and European regulatory authorities with regard to the database likely to be required for CDP 571 marketing approval for acute treatment of active Crohn's disease, and for its ongoing clinical management on an as-needed basis.
Celltech and Biogen, Inc. (Nasdaq: BGEN - News) will review their collaboration on CDP 571 following these discussions with the regulatory authorities.
Further details of the results are as follows:
* CDP 571 showed promising activity against a range of acute endpoints
important in the management of disease flares. The number of
patients attaining the combined endpoint of a CDAI reduction of > or
= 100 points and/or remission was statistically significant at week
2 (p = 0.011) and week 4 (p = 0.014) on an ITT basis.
* Over the 28-week study period CDP 571 achieved a series of clinical
responses relevant to the longer-term management of active disease.
The response across the 28-week period was significant (p = 0.02)
compared to placebo, as assessed by comparing the AUCs (areas under
the curves). The combined primary endpoint at 28 weeks (CDAI
reduction > or = 100 points and/or attainment of remission) was not
met when analyzed on an ITT basis, although there was a trend to
significance (p = 0.067), but was achieved with a per protocol
analysis (p = 0.048).
The second study, conducted over 35 weeks, involved over 270 steroid-dependent patients, and assessed the ability of CDP 571 to enable safe withdrawal of steroids from these patients while maintaining disease remission. Whilst CDP 571 enabled 55% of patients to discontinue steroid usage at the end of the treatment period, there was no significant difference when compared with the placebo group, which displayed an unusually high response rate. Further analyses are ongoing to determine whether CDP 571 treatment demonstrated significant effectiveness in any patient sub-groups.
Very importantly, CDP 571 was well tolerated in both studies, with an excellent safety profile. A very low frequency of immune response was detected in patients over the entire treatment period despite repeated dosing. The overall rates of adverse events were very similar in CDP 571-treated and placebo groups, with no significant differences, including infection rates. In total over 1,000 patients have been treated with CDP 571, with most patients having been treated for 6-12 months.
Contacts:
For Celltech:
Dr. Peter Fellner Chief Executive Officer (44)(0) 1753 534655
Richard Bungay Director Corporate Communications (44)(0) 1753 447930
Katharine Sharkey Brunswick (London) (44)(0) 207 404 5959
Cindy Leggett-Flynn Brunswick (New York) (1)(212) 333 3810
Celltech Group plc (NYSE: CLL; LSE: CCH) is one of Europe's largest biotechnology companies, with an extensive late stage development pipeline and a profitable, cash-generative pharmaceutical business. Celltech also possesses drug discovery capabilities of exceptional strength, including a leading position in antibody engineering.
CDP 571
CDP 571 belongs to a new therapeutic class of medicines that inhibit tumor necrosis factor alpha (TNF-alpha), a key mediator in a number of autoimmune and inflammatory diseases, including rheumatoid arthritis and Crohn's disease. CDP 571 is a second generation, humanized antibody, which binds with high affinity to TNF-alpha.
Crohn's disease
Crohn's disease is a chronic, inflammatory disease of the gastrointestinal tract. Symptoms associated with Crohn's disease include diarrhea, abdominal pain and fever, and can also include fissures, fistulas and abscesses. Loss of appetite and subsequent weight loss also may occur. In addition, certain drugs used to treat the disease may cause side effects, such as high-dose corticosteroid therapy, which can predispose patients to infections, bone thinning (osteoporosis), and fractures. Crohn's disease causes considerable morbidity and up to 25% of patients with active disease may require hospital treatment each year. Approximately 400,000 patients are estimated to have Crohn's Disease in the US and EU.
Crohn's disease is named after Burrill B. Crohn, the first name in a three-author landmark paper published in 1932, which described the disease.
Crohn's Disease Activity Index (CDAI)
The CDAI is the generally accepted and validated composite measure for Crohn's disease clinical trials. It is an assessment of eight different measures, including:
* Abdominal pain rating
* Symptoms related to Crohn's disease, such as arthritis, uveitis,
fistula and febrile (fever) episodes
* Hematocrit (red blood cell count) and biochemical blood markers of
chronic inflammation
* Body weight
A reduction following treatment in the CDAI index of 70 points or more is generally viewed as a clinically significant response, and a CDAI score of 150 or below is generally viewed as representing disease remission. |
