SAN DIEGO, Oct. 26 According to new results from the WELCOME trial, exploratory data analyzing the impact of treatment with CIMZIA(®) (certolizumab pegol) - the only PEGylated anti-TNF (alpha) (Tumor Necrosis Factor alpha) - administered either every two weeks or every four weeks, showed that the majority of Crohn's disease patients in both dosing groups experienced no hospitalizations and surgical procedures during the course of the 26-week study. These exploratory data from the WELCOME trial, which studied patients who had been on the anti-TNF therapy infliximab, but failed or developed a hypersensitivity to the treatment, will be presented this week at the American College of Gastroenterology (ACG) Annual Meeting.
CIMZIA is indicated for reducing the signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. The recommended initial adult dose of CIMZIA is 400mg at Weeks 0, 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks.
In the WELCOME trial, which evaluated moderate to severe Crohn's disease patients who were intolerant to or no longer responding to infliximab therapy, more than 60 percent (329 out of 539 patients enrolled) responded to a 6-week, open label, induction phase with CIMZIA (400 mg subcutaneously at weeks 0, 2, and 4). Patients were then randomized at week 6 to receive CIMZIA (400 mg) every two (q2w) or four (q4w) weeks until week 26 in a double-blind, maintenance comparison phase. Responders were defined as those with a decrease in CDAI score greater than or equal to 100 points from baseline at week 6. The number and length of hospitalizations, number of emergency room visits, and number of medical procedures were recorded during the WELCOME study. The post-hoc analysis of the WELCOME trial evaluated CIMZIA's impact on the incidence of hospitalization and surgical procedures during hospital stays. The majority of patients (86 percent) in both groups (n=139 out of 161 in the q2w group; n=145 out of 168 in the q4w group) underwent no hospitalizations, with ten percent in the q2w group (n=16 out of 161) and nine percent in the q4w group (n=15 out of 168) requiring one hospital stay. (Abstract #P678)
"The data suggest that the recommended 400mg q4w dosing works as well as the accelerated dosing interval in this refractory population, adding to the extensive results from the WELCOME trial," said study investigator Douglas Wolf, M.D., Atlanta Gastroenterology Associates, Atlanta, Ga. "Treatment with CIMZIA may impact the number of hospital visits and related surgeries based on these findings."
There were no statistically significant differences in the mean number of hospital stays (0.193 vs. 0.208; p=0.964), duration of the hospital stay (1.398 vs. 1.679; p=0.986) and surgical procedures performed during hospital stays (0.037 vs. 0.030; p=0.950) between the two CIMZIA treatment groups, as measured by the Wilcoxon signed-rank test.
Additional data from the WELCOME study presented at ACG includes:
"Crohn's is highly individualized and these data provide additional insight into how use of CIMZIA may impact the need for hospitalization or surgery while treating this complicated disease," said David Robinson, vice president and general manager of UCB's Immunology Business Unit.
In previously reported data from the WELCOME study, CIMZIA demonstrated a low incidence of injection site pain, in less than 2% of cases. Common adverse events (AEs) included: headache; nasopharyngitis, or the common cold; nausea; vomiting; pyrexia, or fever; and arthralgia, or joint pain. Serious adverse events (SAEs) were present in 7% of cases, and were most commonly gastrointestinal (5%) or infections and infestations (2%).
Earlier this year, UCB announced that CIMZIA is available to adult moderate to severe Crohn's patients in a pre-filled syringe, developed in partnership with OXO Good Grips(® )for subcutaneous self-administration once every four weeks after initial dosing. 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 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 subcutaneously 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 >=100 points from baseline) at Week 6. Remission was defined as a CDAI score of <=150 points. The secondary endpoints are to assess and compare the clinical efficacy of CIMZIA 400 mg maintenance therapy administered q4w or q2w over 26 weeks; to assess the clinical efficacy of CIMZIA 400 mg as induction and two regimens of maintenance therapy on patient reported outcome scores; to evaluate tolerability and safety of CIMZIA; and to evaluate the effect of certolizumab pegol induction and maintenance therapy on plasma CRP levels.
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). The inflammation may be caused by the presence of high levels of Tumor Necrosis Factor (TNF) found in people with Crohn's disease. 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-TNF (Tumor Necrosis Factor). CIMZIA( )has a high affinity for human TNF-alpha, selectively neutralising 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 immunological diseases. The U.S. Food and Drug Administration (FDA) has approved CIMZIA 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 and for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). CIMZIA was approved in Switzerland for induction of a clinical response and for the maintenance of a clinical response and remission in patients with active Crohn's disease who have not responded adequately to conventional treatment in September 2007. Health Canada and the European Commission have both approved CIMZIA in combination with methotrexate (MTX), for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. UCB is also developing CIMZIA in other autoimmune disease indications. CIMZIA is a registered trademark of UCB PHARMA S.A.
IMPORTANT SAFETY INFORMATION
Risk of Serious Infections
Patients treated with CIMZIA are at an increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. CIMZIA should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:
The risks and benefits of treatment with CIMZIA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Serious and sometimes fatal infection due to bacterial, mycobacterial, invasive fungal, viral or other opportunistic pathogens has been reported in patients receiving TNF-blocking agents. Among opportunistic infections, tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis were the most common. Treatment with CIMZIA should not be initiated in patients with an active infection, including clinically important localized infections. CIMZIA should be discontinued if a patient develops a serious infection or sepsis. Patients who develop a new infection during treatment with CIMZIA should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for immunocompromised patients, and appropriate antimicrobial therapy should be initiated. Appropriate empiric antifungal therapy should also be considered while a diagnostic workup is performed for patients who develop a serious systemic illness and reside or travel in regions where mycoses are endemic.
During controlled and open-labeled portions of CIMZIA studies of Crohn's disease and other diseases , malignancies (excluding non-melanoma skin cancer) were observed at a rate of 0.5 per 100 patient-years among 4,650 CIMZIA-treated patients versus a rate of 0.6 per 100 patient-years among 1,319 placebo-treated patients. 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. In CIMZIA RA clinical trials (placebo-controlled and open label) a total of three cases of lymphoma were observed among 2,367 patients. This is approximately 2-fold higher than expected in the general population. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of TNF blocker therapy in the development of malignancies is not known.
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.
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.
Hepatitis B Reactivation
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, with careful evaluation and monitoring prior to and during treatment. In patients who develop HBV reactivation, discontinue CIMZIA and initiate effective anti-viral therapy with appropriate supportive treatment.
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. 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. 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.
An increased risk of serious infections has been seen in clinical trials of other TNF blocking agents used in combination with anakinra or abatacept. Formal drug interaction studies have not been performed with rituximab or natalizumab; however because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of CIMZIA in these combinations. Therefore, the combination of CIMZIA with anakinra, abatcept, rituximab, or natalizumab 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. CIMZIA may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities.
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 >=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.
In controlled RA clinical trials, the most common adverse events that occurred in >= 3% of patients taking CIMZIA 200 mg every other week with concomitant methotrexate (n=640) and more frequently than with placebo with concomitant methotrexate (n=324) were upper respiratory tract infection (6% CIMZIA, 2% placebo), headache (5% CIMZIA, 4% placebo), hypertension (5% CIMZIA, 2% placebo), nasopharyngitis (5% CIMZIA, 1% placebo), back pain (4% CIMZIA, 1% placebo), pyrexia (3% CIMZIA, 2% placebo), pharyngitis (3% CIMZIA, 1% placebo), rash (3% CIMZIA, 1% placebo), acute bronchitis (3% CIMZIA,1% placebo), fatigue (3% CIMZIA, 1% placebo). Hypertensive adverse reactions were observed more frequently in patients receiving CIMZIA than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs. Patients receiving CIMZIA 400mg as monotherapy every 4 weeks in RA controlled clinical trials had similar adverse reactions to those patients receiving CIMZIA 200mg every other week. The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for CIMZIA and 2.5% for placebo.
Please visit http://cimzia.com/crohns-disease/pdf/Prescribing_Information.pdf for full prescribing information.
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing approximately 10 000 people in over 40 countries, UCB generated revenue of EUR 3.6 billion in 2008. UCB is listed on Euronext Brussels (symbol: UCB).
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.
-- Improvement in work productivity and daily activities by certolizumab pegol in Crohn's disease patients with prior loss of response or intolerance to infliximab (Abstract #P679) -- Efficacy of certolizumab pegol in Crohn's disease patients with secondary failure to infliximab is not affected by concomitant medications (Abstract #P701) -- Regain of response and remission by dose adjustment in patients with Crohn's disease who responded to certolizumab pegol: results from the WELCOME study (Abstract #P699) -- Efficacy of certolizumab pegol is not affected by baseline anti-infliximab antibody status in patients with Crohn's disease with secondary infliximab failure (Abstract #P702)