Cimzia (certolizumab pegol), Significantly Reduces Structural Damage and Rheumatoid Arthritis Signs & Symptoms for Up to One YearTwo Large Phase III Trials Confirm Robust Efficacy of CIMZIA
BOSTON, November 07, 2007 /PRNewswire/ -- UCB announced today the results of new Phase III data from the RAPID 1 and 2 studies presented at the of Rheumatology Annual Scientific Meeting (ACR), which show CIMZIA(R) (certolizumab pegol), the first and only PEGylated Fc-free anti-TNF (Tumor Necrosis Factor), given with methotrexate, is significantly more effective than methotrexate alone for the inhibition of progression of structural joint damage in patients with active rheumatoid arthritis (RA). Also, CIMZIA combined with methotrexate was shown to significantly reduce the signs and symptoms of active RA compared with methotrexate alone for up to one year.
The RAPID 1 data show that CIMZIA, given every two weeks with methotrexate, is significantly more effective for the inhibition of the progression of structural joint damage compared with placebo plus methotrexate at both six and 12 months, as measured in change from mTSS(b) at baseline. Data from RAPID 2 confirm these results, showing that CIMZIA in combination with methotrexate is significantly more effective in inhibiting the progression of structural joint damage compared with placebo plus methotrexate at six months.
"These findings suggest that treatment with certolizumab pegol plus methotrexate can significantly inhibit structural joint damage, which is important for patients who do not respond effectively to methotrexate," explained Edward Keystone, M.D., Rheumatology Department at the University of Toronto. "The data show that certolizumab pegol may lessen debilitating damage and suggest that it has the potential to become an important therapeutic option for patients with RA."
In addition, another study demonstrated the efficacy of CIMZIA in the treatment of the signs and symptoms of RA as a monotherapy, administered every four weeks. "This potential flexibility in dosing could be important for patients," commented Dr. Keystone.
Additional new long-term RAPID 1 data showed that CIMZIA in combination with methotrexate significantly reduced signs and symptoms of active rheumatoid arthritis, compared with placebo plus methotrexate, with sustained results for up to one year. Data from RAPID 2 reinforced these findings, showing that CIMZIA in combination with methotrexate significantly reduced signs and symptoms of active RA compared with placebo plus methotrexate at week 24.
CIMZIA had low occurrence (<5 percent) of treatment discontinuation due to adverse events. The most commonly reported adverse events were headache, nasopharyngitis, cough and abdominal pain. Reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma), consistent with findings from other trials in the anti-TNF class.
In another study presented at the ACR meeting - of current and recently- lapsed users of subcutaneous anti-TNF therapy - injection site pain was identified as a problem by one-third of patients. Approximately a quarter of current users (22 percent), cited injection site pain as problematic. Further, recently-lapsed users (11 percent), cited it as a reason for discontinuation. In the RAPID studies, CIMZIA has been shown to have a low incidence (less than or equal to 2 percent) of injection site pain.
"These results have shown that CIMZIA may provide a valuable treatment option for patients with RA," said Niti Goel, M.D., U.S. Medical Director, Inflammation, UCB. "UCB is committed to continuing to develop novel therapeutics to address patient needs in this chronic and debilitating condition."
Preparation for a regulatory submission for CIMZIA in the treatment of RA is ongoing, with filing planned by the end of 2007.
Further information Alyssa Dargento, Media T: +1-212-453-2121 Antje Witte, Investor Relations T: +32-2-559-9414 Mareike Mohr, Investor Relations T: +32-2-559-9264 Notes to Editors:
RAPID Clinical Trials Program
The RAPID series of clinical trials were designed to establish the efficacy and tolerability of CIMZIA(R) (certolizumab pegol) in the treatment of rheumatoid arthritis. The RAPID clinical trial program is comprised of two large, international, multi-center placebo-controlled studies - RAPID 1 (027) and RAPID 2 (050).
In the year-long RAPID 1 trial, 982 patients were randomly allocated to receive one of three treatment regimens:
-- 393 patients received 400 mg formulation CIMZIA at the start of the study and at weeks two and four, then 200 mg given every two weeks, together with methotrexate; -- 390 patients received 400 mg formulation CIMZIA every two weeks, together with methotrexate; -- 199 patients received placebo every two weeks, together with methotrexate.
In all three arms of the study, the dose of methotrexate was 10 mg per week or greater. Co-primary endpoints for the study RAPID 1 were the ACR20 responder rate(a) at week 24 and the change from baseline in mTSS(b) at week 52.
Six and 12 month ACR responses for RAPID 1 CIMZIA(R) CIMZIA(R) (certolizumab (certolizumab pegol) pegol) Placebo & MTX 200mg & MTX 400mg & MTX Six months ACR 20 13.6 58.8 60.8* ACR 50 7.6 37.1* 39.9* ACR 70 3.0 21.4* 20.6* 12 months ACR 20 13.1 53.1* 54.9* ACR 50 7.6 38.0* 39.9* ACR 70 3.5 21.2* 23.2* Six and 12 month mean mTSS changes from baseline for RAPID 1 CIMZIA(R) CIMZIA(R) (certolizumab (certolizumab pegol) pegol) Placebo & MTX 200mg & MTX 400mg & MTX Six months 1.3 0.2* 0.2* 12 months 2.8 0.4* 0.2* *p<0.001
In the six-month RAPID 2 trial, 619 patients were randomly allocated to receive one of three treatment regimens:
-- 246 patients received 400 mg formulation CIMZIA at the start of the study and at weeks two and four, then 200 mg given every two weeks, together with methotrexate; -- 246 patients received 400 mg formulation CIMZIA every two weeks, together with methotrexate; -- 127 patients received placebo every two weeks, together with methotrexate.
In all three arms of the study the dose of methotrexate was 10mg per week or greater. Patients were assessed for improvement in signs and symptoms of RA. The primary endpoint for the study RAPID 2 was ACR20 responder rate at week 24.
In both studies, CIMZIA given at a dosage of 200mg every two weeks was equally effective as a dosage of 400mg every two weeks.
Six month ACR Responses for RAPID 2 CIMZIA(R) CIMZIA(R) (certolizumab (certolizumab pegol) pegol) Placebo & MTX 200mg & MTX 400mg & MTX ACR 20 8.7 57.3* 57.6* ACR 50 3.1 32.5* 33.1* ACR 70 0.8 15.9** 10.6+ *p<0.001 **p=0.002 +p=0.008 Six month mean mTSS changes from baseline for RAPID 2 CIMZIA(R) CIMZIA(R) (certolizumab (certolizumab pegol) pegol) Placebo & MTX 200mg & MTX 400mg & MTX Six months 1.2 0.2** -0.4* *p<0.001 **p=0.003 (a) ACR ( of Rheumatology) response scores measure improvement in the tender and swollen joint count and also include assessment of the following five parameters: patient's global assessment, physician's global assessment, patient's assessment of pain, degree of disability, and level of acute-phase reactant. ACR20 is achieved when there is 20% improvement in the tender and swollen joint count as well as a 20% improvement in at least three of the five parameters. ACR50 & ACR70 are an extension of these criteria corresponding to a 50% and 70% improvement respectively.(1) (b) Modified Total Sharp Scores (mTSS) is a measurement used to assess changes in bone erosion and joint-space narrowing measured by X-ray. A smaller change in mTSS reflects less progression of joint damage.(2)
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a progressive autoimmune disease that causes chronic inflammation of the joints. It is estimated that five million people suffer from RA globally,(3) with 0.3 percent to 1 percent of the population in industrialized countries suffering from RA.(4)
Prevalence is not split evenly between genders, since women are three times more likely to be affected than men.(5) Although it can affect people of all ages, the onset of RA usually occurs between the ages of 35-55 years.(6)
Symptoms of RA include joint stiffness, joint pain, inflammation of the affected areas and an associated reduction in mobility. These symptoms can be intermittent and vary in severity from patient to patient. In more severe cases RA can eventually lead to disability. RA patients are also at a higher risk of developing other conditions, in particular heart disease, stroke, infections, lung problems and osteoporosis.(7)
As there is currently no cure for RA, treatment goals center on disease management and controlling symptoms. Treatment is aimed at controlling disease progression, providing pain relief and reducing swelling, preventing joint damage and deformity and maintaining function of the affected joints to prevent disability.
Traditional treatments for RA include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease modifying anti-rheumatic drugs (DMARDs), with biological therapies a more recent addition to the list of treatment options. Anti-TNF (TNF-alpha; Tumor Necrosis Factor) therapies are specific types of monoclonal antibodies (biological therapies) which have been used in patients with RA. They may be given alone but are usually given in combination with methotrexate or another immunosuppressant. Anti-TNF therapies have proven to be effective treatments, with the potential to prevent joint damage. They work by inhibiting the action of TNF-alpha, an inflammatory mediator, either directly or indirectly responsible for damaging the joint.(7)
About CIMZIA(R) (certolizumab pegol)
CIMZIA(R) is an investigational drug product. If approved, CIMZIA will be the first and only PEGylated anti-TNF (Tumor Necrosis Factor). CIMZIA is Fc- free and thus avoids potential cellular cytotoxicity in vitro. 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.
UCB filed a BLA with the Food and Drug Administration (FDA) for CIMZIA in the treatment of Crohn's disease on February 28, 2006 and on April 28, 2006 submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) for the same indication. CIMZIA was approved in Switzerland for the treatment of Crohn's disease in September 2007. Preparation for a regulatory submission for CIMZIA in the treatment of RA is ongoing, with filing planned by the end of 2007.
References (1) of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the Management of Rheumatoid Arthritis 2002 update. Arthritis & Rheumatism, 2002 Vol. 46, No. 2 (2) Sharp JT, Lidsky MD, Collins LC, Moreland J. Methods of scoring the progression of radiologic changes in rheumatoid arthritis: Correlation of radiographic, clinical and laboratory abnormalities. Arthritis & Rheumatism, 1971, Vol. 14, No. 6 (3) Stakeholder Insight: Rheumatoid Arthritis, Biologics battle up the treatment algorithm, Data Monitor, 7 September 2006 (4) Woolf AD & Pfleger B, Burden of major musculoskeletal conditions: Bulletin of the World Health Organization 2003, 81 (9) (5) Panayi G What is RA? National Rheumatoid Arthritis Society, June 2006 (6) Hellier, J et al, HLA-DRB1 genes and patients with late onset rheumatoid arthritis, Annals of Rheumatic Disease, 2001;60:531-533 (7) Firestein G, Rheumatoid Arthritis, ACP Medicine WebMD Publishing, August 2004
UCB, Brussels, Belgium (www.ucb-group.com) is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialisation of innovative pharmaceutical and biotechnology products in the fields of central nervous system disorders, allergy/respiratory diseases, immune and inflammatory disorders and oncology - UCB focuses on securing a leading position in severe disease categories. Employing more than 10,000 people in over 40 countries, UCB achieved revenue of 3.5 billion euro in 2006 on a pro forma basis. UCB is listed on the Euronext Brussels Exchange and owns approx. 88% of the shares of SCHWARZ PHARMA AG. SCHWARZ PHARMA AG (Monheim, Germany) is a member of UCB Group.
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.
Posted: November 2007