New Data From REALISTIC Study Showed Cimzia® (certolizumab pegol) Provided Rapid and Sustained Efficacy, Over 28 Weeks, in a Broad Population of Patients With Moderate to Severe Rheumatoid Arthritis (RA) Including Those Who Discontinued Prior Anti-TNF Therapy

BRUSSELS and CHICAGO, Nov. 7, 2011 /PRNewswire/ -- UCB today announced new data which showed that treatment with Cimzia® (certolizumab pegol) was associated with a rapid and sustained clinical response over 28 weeks in a broad population of moderate to severe rheumatoid arthritis (RA) patients. The results, presented during the American College of Rheumatology's (ACR) 2011 Annual Scientific Meeting in Chicago, November 5-9, are from an open-label extension of the REALISTIC (RA EvALuation In Subjects receiving TNF Inhibitor Certolizumab pegol) study, and demonstrated consistent efficacy and improved physical function irrespective of prior anti-TNF therapy, concomitant disease modifying antirheumatic drugs (DMARDs), or duration of disease.

"These results are encouraging because they show that the rapid improvement in disease activity, as a result of the clinical response to certolizumab pegol, is sustained in patients who failed on previous therapies," said co-lead investigator Maxime Dougados, MD, Professor of Rheumatology, Rene Descartes University, Department of Rheumatology B, Cochin Hospital, Paris. "The data from the REALISTIC study is of interest because the trial included a broad RA patient population, which reflects aspects of the diversity we see day-to-day in clinical practice."*

Patients (n=1,063) who had participated in the 12-week randomized, double-blind, placebo-controlled REALISTIC study, either on certolizumab pegol or placebo plus DMARD, were given the option of participating in an open-label extension (OLE) study for a further 16 weeks (28 weeks in total). In total 954 patients entered the extension study and were given certolizumab pegol, including those patients that were previously treated with placebo in the 12-week controlled period of the trial. At Week 28, positive efficacy results were comparable between patients who had received certolizumab pegol for 28 weeks in total and those that switched from placebo to certolizumab pegol after 12 weeks.*  

A total of 770 patients who had previously been given certolizumab pegol, and 184 patients who had been given placebo, entered the extension study. At 28 weeks, ACR20 response rates were 59.7% (n=770) for patients taking certolizumab pegol for 28 weeks and 53.3% (n=184) for those taking it for 16 weeks following the initial placebo phase. DAS28(CRP) remission (DAS28 <2.6) was achieved in 22.9% and 21.7% (p=no significant difference) of patients, respectively, while DAS28(ESR) remission (DAS28 <2.6) was achieved in 15.2% and 11.4% (p=no significant difference) of completers, respectively.

Treatment with certolizumab pegol was associated with rapid and consistent efficacy and sustained improvements in disease activity and physical function up to Week 28 in a diverse group of patients with RA closely resembling those seen in routine clinical practice. Rapid efficacy was also seen across patients receiving concomitant DMARDs at baseline, regardless of the number or type of concomitant DMARDs.

In the placebo controlled portion of the trial, the most common serious infections were lower respiratory tract and lung infections. The most common adverse events were infections and infestations, musculoskeletal and connective tissue disorders, and nervous system disorders. Incidence of adverse in the OLE phase was 305.8 events per 100 patient years in patients randomized to certolizumab pegol in the double blind period compared to 406.2 in patients randomised to placebo and switched to certolizumab pegol in the OLE. Incidence of serious adverse events per 100 patient years was 14.7 vs 16.3, respectively.

* Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.

For further Information:
Scott Fleming, Global Communications Manager – Immunology
T +44 770.277.7378, [email protected]  

Andrea Levin, Senior PR Manager, US Communications and Public Relations
T +1 770 970 8352, [email protected]

Antje Witte, Investor Relations, UCB
T +32.2.559.9414, [email protected]

Michael Tuck-Sherman, Investor Relations, UCB
T +32.2.559.9712, [email protected]  

About REALISTIC

REALISTIC (RA Evaluation in Subjects Receiving TNF Inhibitor Certolizumab Pegol) is a multicenter phase IIIb trial in patients with active rheumatoid arthritis who have shown inadequate response to disease-modifying antirheumatic drugs, including patients with/without prior TNF-inhibitor exposure, with/without concomitant methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs); and varying lengths of disease duration. The study demonstrated that – in a diverse group of RA patients reflecting those seen in daily clinical practice (including those with prior TNF-inhibitor use) – addition of Cimzia® to current therapy was associated with a rapid clinical response consistent in all strata, improved function and reduced disease activity.

A sub-analysis investigated Cimzia® as monotherapy or concomitantly with DMARDs in subgroups of patients with or without prior TNF inhibitor use. Active RA patients with inadequate response to greater than or equal to 1 DMARD were randomized 4:1 to Cimzia® 400mg at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control) every 2 weeks + current therapy. Primary outcome was ACR20 at Week 12. Randomization was stratified by prior TNF inhibitor use, concomitant use of methotrexate (MTX), and disease duration (<2 y vs greater than or equal to 2 y). Treatment effect differences between subgroups were assessed by interactions (treatment by covariate) at 10% significance level.

Active RA patients with inadequate response to greater than or equal to 1 DMARD were randomized 4:1 to CZP 400mg (n=851) at Weeks 0, 2 and 4 followed by 200mg every 2 weeks or placebo injection (control, n=212) every 2 weeks added to current therapy. PROs included fatigue (Fatigue Assessment Scale [FAS; 0–10 numeric rating scale]), pain (0–100mm visual analogue scale [VAS]), and patient's global assessment of disease activity (PtGA, 0–100mm VAS). The minimal clinically important difference (MCID) is a clinically relevant change in a patient's status. The percentage of patients reporting MCIDs was determined: greater than or equal to 1 for FAS, greater than or equal to 6 for MOS-SPI, and greater than or equal to 10mm for pain-VAS and PtGA. Correlations between PROs and DAS28 were also assessed (Pearson correlations [rho], CZP group only).

About CIMZIA®

Cimzia® is the only PEGylated anti-TNF (Tumor Necrosis Factor). 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. 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 moderately to severely active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderately to severely active rheumatoid arthritis. Cimzia® in combination with MTX, is approved in the EU for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.

About UCB

UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8,500 people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2010. UCB is listed on Euronext Brussels (symbol: UCB).

For further information on UCB products, please visit www.UCB.com.

Forward-looking statements

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.

IMPORTANT SAFETY INFORMATION

Risk of Serious Infections and Malignancy

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:

• Active tuberculosis, including reactivation of latent tuberculosis.  Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease.  Patients should be tested for latent tuberculosis before CIMZIA use and during therapy.  Treatment for latent infection should be initiated prior to CIMZIA use.  
• Invasive fungal infections, including histoplasmosis , coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis.  Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease.  Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection.  Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
• Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.

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.

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member.  CIMZIA is not indicated for use in pediatric patients.

Patients treated with CIMZIA are at an increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.  Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers.  Patients have frequently presented with disseminated rather than localized disease.

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 greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (e.g. corticosteroids or methotrexate) may be at a greater risk of infection.  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.

Malignancies

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.

Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy less than or equal to 18 years of age), of which CIMZIA is a member.  Approximately half of the cases were lymphoma (including Hodgkin's and non-Hodgkin's lymphoma, while the other cases represented a variety of different malignancies and included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.  Most of the patients were receiving concomitant immunosuppressants.  

Cases of acute and chronic leukemia have been reported with TNF-blocker use.  Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for developing leukemia.

Heart Failure

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.

Hypersensitivity

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.

Neurologic Reactions

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 central nervous system demyelinating disease, including multiple sclerosis, and with peripheral demyelinating disease, including Guillain-Barre syndrome. 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.

Hematologic Reactions

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.

Drug Interactions

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.

Autoimmunity

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.

Immunizations

Do not administer live vaccines or attenuated vaccines concurrently with CIMZIA.

Adverse Reactions

In controlled Crohn's clinical trials, the most common adverse events that occurred in greater 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.

In controlled RA clinical trials, the most common adverse events that occurred in greater than or equal to  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, 2% 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 consult the full prescribing information in relation to other side effects, full safety and prescribing information: www.cimzia.com

SOURCE UCB

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