UCB 
By Approval represents the fourth U.S. indication for Cimzia®
Brussels (Belgium), 18th October 2013 - (0700 CEST) - regulated information - UCB announced today that the U.S. Food and Drug Administration (FDA) has approved Cimzia® (certolizumab pegol) for the treatment of adults with active ankylosing spondylitis (AS). The FDA also issued a Complete Response Letter relating to the supplemental Biologics License Application (sBLA) of Cimzia® for the treatment of adults with active axial spondyloarthritis (axSpA). UCB is working with the FDA to determine a path forward to bring Cimzia® to US patients living with active axSpA.
With these four indications, UCB confirms expected global peak sales for Cimzia® of at least €1.5 billion during the second half of the decade.
The approval of Cimzia® for adults with active AS was based on a Phase 3, multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of Cimzia® in patients with active axSpA, in which the majority had AS.2
"AS is a lifelong disease that can cause pain and stiffness and at times can be very debilitating for people living with it. Cimzia® provides an important new treatment option for people living with active AS and for rheumatologists. FDA approval of Cimzia® for active AS is an important milestone for UCB and bolsters Cimzia's broad rheumatology portfolio of approved indications in the US," said Professor Dr. Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President, UCB.
In the efficacy and safety study of Cimzia®, patients with active axSpA, including AS, were randomized (1:1:1) to receive Cimzia® 200 mg every two weeks, 400 mg every four weeks or placebo. There were a total of 325 patients in the study, of which 178 had AS. All patients received a loading dose with Cimzia® or placebo at weeks 0, 2 and 4. The primary efficacy variable, the proportion of patients achieving an ASAS20 response rate at week 12, was met with clinical and statistical significance in both dosing arms versus placebo.1
A greater proportion of AS patients treated with Cimzia® 200 mg every two weeks or 400 mg every four weeks achieved ASAS20 response at week 12, compared with AS patients treated with placebo. Responses were similar in patients receiving Cimzia® 200 mg every two weeks and 400 mg every four weeks.1
In this study, adverse events occurred in 70.4% of patients in the Cimzia® group (combined dose) compared to 62.6% of patients in the placebo group. Serious adverse events occurred in 4.7% of patients in both the Cimzia® group (combined dose) and in the placebo group.2 The safety profile for patients with AS treated with Cimzia® was similar to the safety profile seen in patients with RA and in patients with previous experience with Cimzia®. Please see important safety information at the end of this press release for additional details about adverse events associated with Cimzia®.
The FDA recently approved a filing for Cimzia® in the treatment of adults with active psoriatic arthritis (PsA). In the U.S., Cimzia® is also approved for the treatment of adults with moderately to severely active rheumatoid arthritis. In addition, it is approved 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.1
About Cimzia® in Europe
In the EU, Cimzia® in combination with methotrexate (MTX) is approved for the treatment of moderate to severe active rheumatoid arthritis in adult patients inadequately responsive to disease-modifying anti-rheumatic drugs including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.3
In September 2013, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending extending the European Union marketing authorization for the use of Cimzia® in the treatment of adult patients with severe active axSpA. A final decision from the European Commission is expected within two months of the CHMP opinion. The European Medicines Agency is currently reviewing a filing for certolizumab pegol in the treatment of adult patients with active PsA.
About axSpA and AS
axSpA is an inflammatory rheumatic disease that mostly affects the spine and sacroiliac joints.4 axSpA can be further divided into ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA), depending on the presence or absence of definitive changes on x-ray in the sacroiliac joints (SIJ).5
Ankylosing Spondylitis, or AS, is a chronic inflammatory rheumatic disease of the spine6 and is the most well-recognized subset of axSpA.7 The symptoms of AS can vary, but most people experience back pain and stiffness due to inflammation which can proceed to fusion of the sacroiliac joints.4 The condition usually begins between 15 and 35 years of age6, with prevalence estimated to be .5% of the U.S. population.8 AS is more common in men than in women.6 Ankylosing spondylitis has a genetic component and is associated with the HLA-B27 gene.7
IMPORTANT SAFETY INFORMATION ABOUT CIMZIA® IN THE US
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
