UCB announces start of the EXXELERATE™ clinical study in rheumatoid arthritis

Brussels, Belgium, 21 December 2011, 0700 CET – UCB today announced the start of the EXXELERATE™ study which will evaluate the short- and long-term efficacy of Cimzia® (certolizumab pegol) plus methotrexate (MTX) compared with that of Humira®* (adalimumab) plus MTX in the treatment of moderate to severe rheumatoid arthritis (RA). The start of this study confirms previously announced plans.

"This head-to-head study is an important milestone. We believe that EXXELERATE™ should help to provide additional evidence to support early, informed management decisions for people living with this chronic, progressive disease," said Professor Dr Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President UCB.

The primary objectives of the study are to compare the relative efficacy of the two anti-TNF therapies during short- and long-term treatment (12 and 104 weeks respectively).

"While meta-analyses from placebo controlled trials suggest differences in efficacy among anti-TNFs in RA, results from the EXXELERATE™ study should help to provide additional insights to support the current lack of head-to-head data and to guide treatment decisions.” said Roy Fleischmann, MD, Clinical Professor of Medicine, The University of Texas South Western Medical Centre, Dallas, Texas, US. “As recent guidelines on biological agents recommend rapid treatment to target for RA patients, it is also timely for EXXELERATE™ to explore the comparative long term benefits of anti-TNF therapies, related to early response-driven treatment decisions.”

The European League Against Rheumatism (EULAR) and the international Treat-to-Target Expert Committee recommend appropriate therapeutic adaptation of disease-modifying anti-rheumatic drugs to reach targets of remission or low disease activity within three to six months of starting treatment.^1,2

Persistent active disease is a predisposing factor of subsequent disease severity, such as progressive joint damage, irreversible disability and increased mortality.^3-6 Therefore, stopping inflammation rapidly can be an important therapeutic goal and studies have shown that achieving control of disease activity, ideally rapid control, has led to improved long-term outcomes for patients with RA.^7,8

EXXELERATE™ is a multi-centre, single-blind, randomized, parallel-group study which will randomise patients to either certolizumab pegol plus MTX or adalimumab plus MTX. After 12 weeks, patients who respond will continue their initial treatment whereas non-responders will switch to the alternative treatment arm until study end at 104 weeks. By including a week 12 response-based therapeutic decision, EXXELERATE™ aims to assess the impact of early response-driven treatment on long-term (104 weeks) clinical and patient outcomes. The study aims to enroll approximately 900 adult patients with moderate-to-severe RA in multiple geographies including USA, Canada and Europe, who have inadequately responded to MTX and who have not previously received anti-TNF treatment. The headline results from the study are expected in 2016.

* Humira® is a registered trademark of Abbott

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), 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, moderate to severe heart failure.

Before initiation of therapy with Cimzia®, all patients must be evaluated for both active and inactive (latent) tuberculosis infection. Monitor patients closely for signs and symptoms of infections including tuberculosis before, during and after treatment with Cimzia®. If an infection develops, monitor carefully and stop Cimzia® if infection becomes serious.

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®. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended. Carriers of HBV who require treatment with Cimzia® should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop 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(6):964-75.
2. Smolen et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis (2010);69(4):631-7.
3. Wolfe F, Michaud K, Gefeller O, et al. Predicting mortality in patients with rheumatoid arthritis. Arthritis & Rheumatism (2003);48:1530–1542
4. Pincus T, Callahan LF, Sale WG, et al. Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis & Rheumatism (2005);27:864 – 872
5. Wolfe F, Mitchell DM,. Sibley JT et al. The mortality of rheumatoid arthritis. Arthritis & Rheumatism (2005);37: 481–494
6. National Rheumatoid Arthritis Society – What is RA? [Online] Available at: http://www.nras.org.uk/about_rheumatoid_arthritis/what_is_ra/what_is_ra.aspx [Accessed 16 May 2011]
7. 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
8. 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
Antje Witte, Investor Relations UCB
T +32.2.559.9414, antje.witte@ucb.com
France Nivelle, Global Communications, UCB
T +32.2.559.9178, france.nivelle@ucb.com
Eimear O Brien, Director, Brand Communications
T +32.2.559.9271, Eimear.obrien@ucb.com
Andrea Levin, Senior PR Manager, US Communications and Public Relations
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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