UCB announced today the online publication of pivotal study results showing CIMZIA® (certolizumab pegol), the only PEGylated anti-TNF (Tumor Necrosis Factor) together with methotrexate (MTX) rapidly reduced symptoms of disease and inhibited progression of joint damage in adult patients with active rheumatoid arthritis (RA), with sustained results for up to one year. The RAPID (RA PreventIon of structural Damage) 1 study data is published in Arthritis & Rheumatism, the peer-reviewed journal of the American College of Rheumatology.
Both co-primary endpoints, which included the ACR20 responder rate at Week 24 and the change from baseline in the modified Total Sharp Score (mTSS) at Week 52, were met in the one-year study. Patients in both CIMZIA® together with MTX treatment arms were shown to have a significantly higher ACR20 response at 24 weeks (p<0.001) compared with patients receiving placebo together with MTX. In addition, radiographic data showed CIMZIA® together with MTX inhibited progression of RA, with a significantly smaller change from baseline in mTSS at 24 and 52 weeks of treatment, compared with MTX alone (p<0.001).
“In the RAPID 1 study, CIMZIA® together with methotrexate had a rapid onset of action and inhibited structural damage early in adults with rheumatoid arthritis. This demonstrated a clear therapeutic benefit for patients with a reduction in swollen and tender joints, pain and fatigue as early as one week after treatment, and signs of preventing long-term structural damage by 16 weeks,” said lead investigator Edward Keystone, M.D., The Rebecca MacDonald Center for Arthritis, Mount Sinai Hospital, The University of Toronto.
The one-year study showed CIMZIA® together with MTX had a rapid and significant effect in reducing the signs and symptoms of active RA as early as week one, as shown by a significant difference in ACR20 and 50 responses with CIMZIA® compared with placebo, by Week 1 and Week 2 respectively (p<0.001 and p<0.01). Peak responses achieved at 12 and 14 weeks were sustained throughout the study.
Patients treated with CIMZIA® together with MTX experienced significant improvements in physical function and quality of life from Week 1 and sustained for up to one year, measured by mean change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) scores (p<0.001).
Radiographic data showed a significant difference between CIMZIA® together with MTX and placebo treatment arms, which was observed as early as 16 weeks in clinical non-responders (p<0.001).
“CIMZIA® is the first anti-TNF to demonstrate such early results in disease progression. UCB looks forward to bringing these benefits to people who suffer from RA once the regulatory review process is completed,” said Iris Loew-Friedrich, M.D., Ph.D., Chief Medical Officer, UCB.
RAPID 1 and a simultaneous study, RAPID 2, are the first large, placebo-controlled Phase III trials demonstrating the efficacy and tolerability of CIMZIA® in the treatment of RA, as part of a clinical trials program involving more than 2,300 patients.
The most commonly reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma). The most commonly reported adverse events were headache, nasopharyngitis, and upper respiratory tract infections. Pooled safety data from both studies showed that the incidence of injection site burning and stinging (n=<3 new cases/100 years) and discontinuations due to adverse events (AEs) were low in the CIMZIA® group.
“The early, significant and sustained responses seen in the primary dimensions most negatively impacting patients with rheumatoid arthritis could make CIMZIA® an important new treatment option in the U.S., bringing relief for a debilitating disease affecting approximately 1.3 million Americans,” said RAPID 1 investigator Philip Mease, M.D., Director of Rheumatology Research, Swedish Medical Center in Seattle.
About RAPID 1
The double-blind placebo-controlled trial, involving 982 adults, was designed to establish the efficacy and tolerability of CIMZIA® together with MTX, in the treatment of active RA in patients who did not adequately respond to conventional treatment. Patients were randomly allocated to receive one of three treatment regimens: 393 patients received CIMZIA® 400 mg and at Weeks 0, 2 and 4, then 200 mg every two weeks; 390 patients received CIMZIA® 400 mg every 2 weeks; 199 patients received placebo every 2 weeks. RAPID 1 met co-primary endpoints: ACR20 response rate at Week 24 and change from baseline in mTSS at Week 52.
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, with 0.3 percent to 1 percent of the population in industrialized countries suffering from RA. It is estimated that, approximately 1.3 million people in the United States have RA. Women are three times more likely to be affected than men. Although it can affect people of all ages, the onset of RA usually occurs between the ages of 35-55.
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.
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 antirheumatic drugs (DMARDs), with biological therapies a more recent addition. Anti-TNF (TNF-alpha; Tumor Necrosis Factor) therapies are specific types of 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. They work by inhibiting the action of TNF-alpha, an inflammatory mediator, either directly or indirectly responsible for damaging the joint.
About CIMZIA® (certolizumab pegol)
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.
UCB submitted a Marketing Authorisation Application to the European Medicines Agency in June 2008 requesting the approval of CIMZIA® as a subcutaneous treatment for adults with moderate to severe active RA. The US Food and Drug Administration (FDA) has approved CIMZIA® (certolizumab pegol), for reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderate to severe active disease who have an inadequate response to conventional therapy. CIMZIA® was approved in Switzerland for the induction of a clinical response and for the maintenance of a clinical response and remission in patients with active Crohn’s disease who have not responded adequately to conventional treatment. CIMZIA® is currently under review by the FDA for the treatment of adult patients with active rheumatoid arthritis (RA). CIMZIA® is a registered trademark of UCB PHARMA S.A. Please visit http://www.ucb-group.com for full prescribing information for CIMZIA®.
Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation), invasive fungal infections, and other opportunistic infections, have been observed in patients receiving CIMZIA®. Some of these infections have been fatal. Anti-tuberculosis treatment of patients with latent tuberculosis infection reduces the risk of reactivation in patients receiving treatment with TNF blockers such as CIMZIA®. However, active tuberculosis has developed in patients receiving CIMZIA® whose tuberculin test was negative. Evaluate patients for tuberculosis risk factors and test for latent tuberculosis infection prior to initiating CIMZIA® and during therapy. Initiate treatment of latent tuberculosis infection prior to therapy with CIMZIA®. Monitor patients receiving CIMZIA® for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis infection. Consider anti-tuberculosis therapy prior to initiation of CIMZIA® in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Serious infections, sepsis, and cases of opportunistic infections, including fatalities, have been reported in patients receiving TNF blockers, including CIMZIA®. Infections have been reported in patients receiving CIMZIA® alone or in conjunction with immunosuppressive agents. Do not initiate treatment with CIMZIA® in patients with active infections, including chronic or localized infections. Patients who develop a new infection while undergoing treatment with CIMZIA® should be monitored closely. Discontinue administration of CIMZIA® if a patient develops a serious infection. Exercise caution when considering the use of CIMZIA® in patients with a history of recurrent infection, concomitant immunosuppressive therapy, or underlying conditions that may predispose them to infections, or patients who have resided in regions where tuberculosis and histoplasmosis are endemic.
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. Patients who are carriers of HBV and require treatment with CIMZIA® should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, discontinue CIMZIA® and initiate effective anti-viral therapy with appropriate supportive treatment.
During controlled and open-labeled portions of CIMZIA® studies of Crohn’s disease and other investigational uses, malignancies were observed at a rate (95% confidence interval) of 0.6 (0.4, 0.8) per 100 patient-years among 4,650 CIMZIA®-treated patients verses a rate of 0.6 (0.2, 1.7) per 100 patient-years among 1,319 placebo-treated patients. The size of the control group and limited duration of the controlled portions of the studies preclude the ability to draw firm conclusions. 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. The potential role of TNF blocker therapy in the development of malignancies is not known.
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.
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 demyelinating disease. Rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with CIMZIA®; the causal relationship to CIMZIA® remains unclear. Exercise caution in considering the use of CIMZIA® in patients with these disorders.
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®. The causal relationship of these events to CIMZIA® remains unclear. 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.
Serious infections were seen in clinical studies with concurrent use of anakinra (an interleukin-1 antagonist) and another TNF blocker, with no added benefit. Therefore, the combination of CIMZIA® and anakinra 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.
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.
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.
Do not administer live vaccines or attenuated vaccines concurrently with CIMZIA®.
In controlled Crohn’s clinical trials, the most common adverse events that occurred in ³5% 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.
CIMZIA® should be administered by a healthcare professional.
UCB, Brussels, Belgium (http://www.ucb-group.com) is a global leader in the biopharmaceutical industry dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing around 12,000 people in over 40 countries, UCB achieved revenue of 3.6 billion euro in 2007. UCB is listed on Euronext Brussels (symbol: UCB). UCB’s U.S. headquarters is located in Atlanta, Ga. http://www.ucb-group.com
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.