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ORLANDO, Fla. Oct. 7 /PRNewswire-FirstCall/ -- Data from two studies presented this week by UCB at the American College of Gastroenterology (ACG) Annual Meeting demonstrate that CIMZIA(R) (certolizumab pegol) - the only PEGylated anti-TNF alpha (Tumor Necrosis Factor alpha) - provides sustained improvement in symptoms with stable dosing for adult patients suffering from moderate to severe Crohn's disease (CD). A third study presented by UCB provided an estimated comparison of treatment costs and found that CIMZIA offers a cost savings versus other commonly-used biologics.
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An analysis of the PRECiSE 3 open-label extension study data showed that after 2.5 years (30 months) of treatment with CIMZIA, 72 percent of patients were in remission based upon responder analysis. These clinical trial data will be presented by William Sandborn, M.D., of the Mayo Clinic in Rochester, Minn., a study investigator. Previously, UCB had reported remission data up to 18 months.
Furthermore, data from the WELCOME study showed that 39 percent of patients who responded to CIMZIA treatment after failing infliximab therapy achieved clinical remission within six weeks. Additionally, there were no differences in clinical response rates regardless of the reason for infliximab failure, and irrespective of treatment as a monotherapy or in combination with other common Crohn's disease medications.
CIMZIA, manufactured by UCB, was approved by the U.S. Food and Drug Administration on April 22, 2008 for reducing signs and symptoms of moderate to severe Crohn's disease and maintaining clinical response in adult patients who have had an inadequate response to conventional therapy. The approval was based on safety and efficacy data from clinical trials in more than 1,500 patients with Crohn's disease.
WELCOME Study (Abstract #P283)
Data from the Phase IIIb WELCOME study showed that 39 percent of patients who responded to CIMZIA treatment after failing infliximab therapy achieved clinical remission at Week 6 as measured by the Crohn's Disease Activity Index (CDAI). In addition, the study found that 61 percent of study patients reduced CDAI symptom scores by 100 points and 68 percent reduced CDAI scores by 70 points. The CDAI is a patient/physician questionnaire which incorporates eight CD-related variables. Scores of <150 indicate remission, and scores of >450 indicate severe illness along the 600 point scale.
Response to CIMZIA was similar when used as a monotherapy or with concomitant corticosteroids or immunosuppressants. There were also no differences in clinical responses to CIMZIA among those patients who had previously lost response to infliximab (62 percent), were hypersensitive to infliximab (61 percent) or both (58 percent).
PRECiSE 3 Study (Abstract #P280)
The PRECiSE 3 (P3) open-label extension study of PRECiSE 1 and PRECiSE 2 was designed to evaluate the longer-term safety and effectiveness of CIMZIA in patients completing the other two studies. The 30-month analysis includes data from 141 patients who have been continuously treated with CIMZIA for 2.5 years. At the beginning of P3, 73 percent of CIMZIA-treated patients were in remission. After 2.5 years (30 months) of treatment with CIMZIA, 72 percent of patients were in remission based upon responder analysis. The incidence of injection site pain was low in the CIMZIA group, and no new safety signals observed over 2.5 years of active treatment.
Pharmacoeconomics Study (Abstract #P277)
A cost analysis for induction and maintenance dosing regimens for CIMZIA, infliximab and adalimumab was estimated for a 65kg patient over a two-year period. Response and remission rates were assumed the same between treatments, and maintenance therapy was followed if responding to initial therapy and continued in year 2 for remitters. Based on average wholesale prices for the treatments, estimate of treatment costs showed that CIMZIA provided more cost savings during induction and maintenance phases of treatment when compared to infliximab and adalimumab.
A cohort budget analysis, with uptakes of 60 percent, 30 percent and 10 percent in year 1 and 50 percent, 30 percent and 20 percent in year 2 for infliximab, adalimumab and CIMZIA, respectively, was performed for a healthcare plan of 5 million members with a CD prevalence of 162 per 100,000 and incidence rate of 9.6 per 100,000. Results showed that access to CIMZIA provided a savings of more than $1.5 million compared to a healthcare plan that did not include CIMZIA. The data suggest that based on standard regimens for each of the TNF alpha blockers for CD, CIMZIA may be less costly than the two biologics studied.
About WELCOME
The WELCOME study is a 539 patient Phase IIIb multicenter 26-Week trial Evaluating the clinical benefit and tolerability of certoLizumab pegol induCtiOn and Maintenance in patients suffering from Crohn's disease with prior loss of response or intolErance to infliximab. It consists of an open-label induction phase (400 mg of CIMZIA sub-cutaneously at Weeks 0, 2 and 4) and a double-blind maintenance period (400 mg of CIMZIA every 2 or 4 weeks from Week 6). The primary endpoint was defined as the rate of response (defined as a decrease in CDAI score less than or equal to 100 points from baseline) at Week 6. Remission was defined as a CDAI score of greater than or equal to 150 points. After the induction period, 62 percent of patients achieved response and 39 percent achieved remission. One-third of patients had responded to treatment by Week 2 (33 percent) and more than forty percent (44 percent) had responded by Week 4.
About the PRECiSE Clinical Trial Program
PRECiSE, one of the largest, most comprehensive development programs for an anti-TNF for Crohn's disease is composed of two placebo-controlled studies and two open-label safety follow-up studies. In 2007, the two former studies were published in the New England Journal of Medicine (NEJM). The studies demonstrated that patients with moderate to severe Crohn's disease achieved and sustained clinical response with CIMZIA for up to six months, compared to placebo. The safety and tolerability of CIMZIA was consistent with that expected of an anti-TNF agent. In the first follow-up study, patients completing both initial studies are to be given CIMZIA every four weeks for up to seven years. In the second follow-up study, patients who relapsed in either initial study (defined as an increase in CDAI of >70 or absolute CDAI of >350) were re-introduced to CIMZIA every four weeks to be continued for up to seven years, with a single additional dose at week 2.
About Crohn's Disease
Crohn's disease is a chronic, progressive, destructive disorder that causes inflammation of the gastrointestinal (GI) tract, most commonly at the end of the small intestine (the ileum) and beginning of the large intestine (the colon). If not effectively treated, it may result in the need for surgery and hospitalization. Crohn's disease has been estimated to affect as many as half a million Americans. People with Crohn's can experience an ongoing cycle of flare-up and remission throughout their lives. Together with ulcerative colitis, Crohn's disease is an inflammatory bowel disease (IBD).
About CIMZIA (certolizumab pegol)
CIMZIA is the only PEGylated anti-TNFa (Tumour Necrosis Factor). CIMZIA is an effective, rapid-acting and long lasting treatment option for people with RA. 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. UCB is developing CIMZIA in rheumatoid arthritis and other autoimmune disease indications. CIMZIA was approved in April 2008 for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderate to severe active disease who have had an inadequate response to conventional therapy. CIMZIA is a registered trademark of UCB PHARMA S.A. For full prescribing information, please visit www.ucb-group.com.
Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation), invasive fungal infections, and other opportunistic infections, have been observed in patients receiving CIMZIA. Some of these infections have been fatal. Anti-tuberculosis treatment of patients with latent tuberculosis infection reduces the risk of reactivation in patients receiving treatment with TNF blockers such as CIMZIA. However, active tuberculosis has developed in patients receiving CIMZIA whose tuberculin test was negative. Evaluate patients for tuberculosis risk factors and test for latent tuberculosis infection prior to initiating CIMZIA and during therapy. Initiate treatment of latent tuberculosis infection prior to therapy with CIMZIA. Monitor patients receiving CIMZIA for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis infection. Consider anti-tuberculosis therapy prior to initiation of CIMZIA in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Serious infections, sepsis, and cases of opportunistic infections, including fatalities, have been reported in patients receiving TNF blockers, including CIMZIA. Infections have been reported in patients receiving CIMZIA alone or in conjunction with immunosuppressive agents. Do not initiate treatment with CIMZIA in patients with active infections, including chronic or localized infections. Patients who develop a new infection while undergoing treatment with CIMZIA should be monitored closely. Discontinue administration of CIMZIA if a patient develops a serious infection. Exercise caution when considering the use of CIMZIA in patients with a history of recurrent infection, concomitant immunosuppressive therapy, or underlying conditions that may predispose them to infections, or patients who have resided in regions where tuberculosis and histoplasmosis are endemic.
Use of TNF blockers, including CIMZIA may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. Some cases have been fatal. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating CIMZIA therapy. Exercise caution in prescribing CIMZIA for patients identified as carriers of HBV. Patients who are carriers of HBV and require treatment with CIMZIA should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, discontinue CIMZIA and initiate effective anti-viral therapy with appropriate supportive treatment.
During controlled and open-labeled portions of CIMZIA studies of Crohn's disease and other investigational uses, malignancies were observed at a rate (95% confidence interval) of 0.6 (0.4, 0.8) per 100 patient-years among 4,650 CIMZIA-treated patients verses a rate of 0.6 (0.2, 1.7) per 100 patient-years among 1,319 placebo-treated patients. The size of the control group and limited duration of the controlled portions of the studies preclude the ability to draw firm conclusions. In studies of CIMZIA for Crohn's disease and other investigational uses, there was one case of lymphoma among 2,657 CIMZIA-treated patients and one case of Hodgkin lymphoma among 1,319 placebo-treated patients. The potential role of TNF blocker therapy in the development of malignancies is not known.
Symptoms compatible with hypersensitivity reactions, including angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria, have been reported rarely following CIMZIA administration. If such reactions occur, discontinue further administration of CIMZIA and institute appropriate therapy.
Use of TNF blockers, including CIMZIA, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with CIMZIA; the causal relationship to CIMZIA remains unclear. Exercise caution in considering the use of CIMZIA in patients with these disorders.
Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) has been infrequently reported with CIMZIA. The causal relationship of these events to CIMZIA remains unclear. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on CIMZIA. Consider discontinuation of CIMZIA therapy in patients with confirmed significant hematologic abnormalities.
Serious infections were seen in clinical studies with concurrent use of anakinra (an interleukin-1 antagonist) and another TNF blocker, with no added benefit. Therefore, the combination of CIMZIA and anakinra is not recommended.
Interference with certain coagulation assays has been detected in patients treated with CIMZIA. There is no evidence that CIMZIA therapy has an effect on in vivo coagulation.
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. CIMZIA has not been formally studied in patients with CHF. Exercise caution when using CIMZIA in patients who have heart failure and monitor them carefully.
Treatment with CIMZIA may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms of lupus-like syndrome develop.
Do not administer live vaccines or attenuated vaccines concurrently with CIMZIA.
In controlled Crohn's clinical trials, the most common adverse events that occurred in less than or equal to 5% of CIMZIA patients (n=620) and more frequently than with placebo (n=614) were upper respiratory infection (20% CIMZIA, 13% placebo), urinary tract infection (7% CIMZIA, 6% placebo), and arthralgia (6% CIMZIA, 4% placebo). The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for CIMZIA and 7% for placebo.
CIMZIA should be administered by a healthcare professional.
About UCB
UCB, Brussels, Belgium (www.ucb-group.com) is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing around 12 000 people in over 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB is listed on Euronext Brussels (symbol: UCB).
Forward-Looking Statement
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. Such statements are subject to risks and uncertainties that may cause actual results to be materially different from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, effects of future judicial decisions, changes in regulation, exchange rate fluctuations and hiring and retention of its employees.
SOURCE UCB
