UCB announces start of C-EARLY™ study for Cimzia® (certolizumab pegol) in rheumatoid arthritis

BRUSSELS, February 22, 2012 – 0700 CET - UCB today announced the start of C- EARLY™ – a phase III study that will evaluate the efficacy and safety of Cimzia^® (certolizumab pegol) in combination with methotrexate (MTX) for inducing and sustaining clinical response in adults with early, progressive, active, moderate to severe rheumatoid arthritis (RA), who have not previously been treated with disease-modifying antirheumatic drugs (DMARDs). The study also aims to assess whether the frequency of certolizumab pegol administration can be reduced after sustained low disease activity* has been achieved. C-EARLY™ will evaluate patients in the early stage of their disease, that is less than one year since diagnosis.

"We are pleased to announce the start of this study which focuses on treatment for people with early active RA and reflects our continuing commitment to improving the lives of patients at all stages of this severe, progressive disease," said Professor Dr Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President, UCB.

The European League Against Rheumatism (EULAR) recommends that DMARD treatment of RA should aim to achieve remission or low disease activity as soon as possible in every patient and that, once remission has been achieved, tapering of treatment can be considered¹. Research has shown that achieving early control of disease activity can improve long term outcomes for patients with RA^2,3.

“There is growing evidence to support the value of detecting and treating rheumatoid arthritis patients as soon as possible after the onset of disease in order to prevent disease progression. By rapidly achieving the target of sustained remission early in the course of RA, drug-free remission could become an achievable goal,” said Professor Paul Emery, Professor of Rheumatology, University of Leeds, UK. “With C-EARLY™ we are starting an important study which should inform all stakeholders including patients, rheumatologists and payers how to optimize anti-TNF treatment in patients with early RA who have achieved sustained low disease activity.”

C-EARLY™ is a phase III, multi-centre, randomized, double-blind, placebo-controlled study which will randomise patients diagnosed with early, moderate to severe RA to certolizumab pegol plus methotrexate (MTX) or placebo plus MTX for 52 weeks. Patients who achieve sustained remission with certolizumab pegol at week 52 will be re-randomized to varying reduced doses of certolizumab pegol or withdrawn from certolizumab for a further 52 weeks. The co-primary efficacy variables are the proportion of patients reaching sustained remission** at week 52, and the proportion of patients who maintain low disease activity between week 52 and week 104. The study aims to enrol approximately 800 adult patients in the U.S., Canada and Europe with early, progressive, active, moderate to severe RA who are naïve to DMARDs. Headline results for the study are expected in 2016.

*Sustained low disease activity defined as Disease Activity Score 28[ESR]≤3.2 at week 40 and week 52 visits
**Sustained remission defined as Disease Activity Score 28[ESR]<2.6 at week 40 and week 52 visits

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.

Cimzia® (certolizumab pegol) in European Union/ EEA important safety information
Cimzia® was studied in 2367 patients with RA in controlled and open label trials for up to 57 months. The commonly reported adverse reactions (1-10%) in clinical trials with Cimzia® and post-marketing were viral infections (includes herpes, papillomavirus, influenza), bacterial infections (including abscess), rash, headache (including migraine), asthenia, leukopaenia (including lymphopaenia, neutropaenia), eosinophilic disorder, pain (any sites), pyrexia, sensory abnormalities, hypertension, pruritis (any sites), hepatitis (including hepatic enzyme increase) and injection site reactions. Serious adverse reactions include sepsis, opportunistic infections, tuberculosis, herpes zoster, lymphoma, leukaemia, solid organ tumours, angioneurotic edema, cardiomyopathies (includes heart failure), ischemic coronary artery disorders, pancytopaenia, hypercoagulation (including thrombophlebitis, pulmonary embolism), cerebrovascular accident, vasculitis, hepatitis/hepatopathy (includes cirrhosis), and renal impairment/nephropathy (includes nephritis). In RA controlled clinical trials, 5% of patients discontinued taking Cimzia® due to adverse events vs. 2.5% for placebo.

Cimzia® is contraindicated in patients with hypersensitivity to the active substance or any of the excipients, active tuberculosis or other severe infections such as sepsis or opportunistic infections or moderate to severe heart failure.

Serious infections including sepsis, tuberculosis and opportunistic infections have been reported in patients receiving Cimzia®. Some of these events have been fatal. Monitor patients closely for signs and symptoms of infections including tuberculosis before, during and after treatment with Cimzia®. Treatment with Cimzia must not be initiated in patients with a clinically important active infection. If an infection develops, monitor carefully and stop Cimzia® if infection becomes serious. Before initiation of therapy with Cimzia®, all patients must be evaluated for both active and inactive (latent) tuberculosis infection. If active tuberculosis is diagnosed prior to or during treatment, Cimzia® therapy must not be initiated and must be discontinued. If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before initiating treatment with Cimzia®. Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, wasting/weight loss, low grade fever, listlessness) suggestive of tuberculosis occur during or after therapy with Cimzia®.

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Cimzia® who are chronic carriers of the virus (i.e. surface antigen positive). Some cases have had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with Cimzia®. Carriers of HBV who require treatment with Cimzia® should be closely monitored and in the case of HBV reactivation Cimzia® should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.

TNF antagonists including Cimzia® may increase the risk of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease; of formation of autoantibodies and uncommonly of the development of a lupus-like syndrome; of severe hypersensitivity reactions. If a patient develops any of these adverse reactions, Cimzia® should be discontinued and appropriate therapy instituted.

With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF antagonist cannot be excluded. Rare cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have been reported in patients treated with Cimzia®.

Adverse reactions of the hematologic system, including medically significant cytopenia, have 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 haematological abnormalities.

The use of Cimzia® in combination with anakinra or abatacept is not recommended due to a potential increased risk of serious infections. As no data are available, Cimzia® should not be administered concurrently with live vaccines or attenuated vaccines. The 14-day half-life of Cimzia® should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Cimzia® should be closely monitored for infections.

Please consult the full prescribing information in relation to other side effects, full safety and prescribing information. European SmPC date of revision November 2011.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069763.pdf

References
1. Smolen J et al. EULAR recommendation for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis (2010);69:964-75.
2. Smolen JS, Han C, van der Heijde D, et al. Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade. Ann Rheum Dis (2009) 68:823–827.
3. Van der Heijde D, Schiff M, Keystone E, et al. Time to and level of initial DAS28 change with certolizumab pegol predicts the likelihood of having low disease activity at years 1 and 2 in patient with rheumatoid arthritis. Ann Rheum Dis (2010);69(Suppl3):505.

For further information
France Nivelle, Global Communications, UCB
T +32.2.559.9178, france.nivelle@ucb.com
Antje Witte, Investor Relations UCB
T +32.2.559.9414, antje.witte@ucb.com
Eimear O Brien, Director, Brand Communications, UCB
T +32.2.559.9271, eimear.obrien@ucb.com
Andrea Levin, Senior PR Manager, US Communications and Public Relations, UCB
T +1 770 970 8352, andrea.levin@ucb.com

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).

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