Healthcare Industry News: hepatitis B virus
News Release - October 27, 2008
CIMZIA(R) (Certolizumab Pegol) Provides Rapid and Sustained Relief from Signs and Symptoms of Rheumatoid Arthritis for Two YearsCIMZIA(R) Data Shows Long-term Improvements in Productivity, Quality of Life and Lessened Fatigue According to Studies Presented at American College of Rheumatology (ACR) Annual Scientific Meeting
SAN FRANCISCO, Oct. 27 -- (Healthcare Sales & Marketing Network) -- 5:00 AM PST -- UCB announced today results from several Phase III clinical trials evaluating CIMZIA® (certolizumab pegol) - the only PEGylated anti-TNF (Tumor Necrosis Factor) - presented at the American College of Rheumatology (ACR) Annual Scientific Meeting. Results from the open-label extension study to RAPID 1 met both co-primary endpoints (American College of Rheumatology (ACR) 20 response(a) scores at Week 24 and change from baseline in modified Total Sharp Scores at Week 52). Results also showed that CIMZIA together with methotrexate (MTX) provided ACR 20 response as early as Week 1 with sustained long-term benefit in relieving symptoms of rheumatoid arthritis (RA) through 100 weeks.
Another analysis investigating the rapidity of response to CIMZIA as a monotherapy (FAST 4WARD) and together with MTX (RAPID 1) was presented at the meeting. Both studies met their primary endpoints (ACR20 response rate at Week 24) with clinical and statistical significance. The analysis presented showed that the response to CIMZIA treatment was rapid in both studies with more than a third (36.7 percent) of patients receiving CIMZIA as a monotherapy (FAST 4WARD) and nearly a quarter (22.9 percent) of patients receiving CIMZIA together with MTX (RAPID 1) achieving an ACR20 response within one week, both significantly different from placebo. ACR20 response rates peaked at Week 12 in both studies and were sustained until the end of the studies (Week 24 in FAST 4WARD; Week 52 in RAPID 1).
"The data show that treatment with CIMZIA in clinical trials produced a fast and clinically meaningful effect for RA patients over an extended period of time," said Michael Schiff, M.D., study investigator and Clinical Professor of Medicine at the University of Colorado School of Medicine.
CIMZIA had a low occurrence of treatment discontinuation due to adverse events. The most commonly occurring adverse events were headache, nasopharyngitis, and upper respiratory tract infections. Pooled safety data from the two main phase III trials showed there was a low incidence of injection site burning and stinging (n=<3 new cases /100 patient-years) and a low level of discontinuations due to adverse events (AEs). Reported serious adverse reactions were infections (including tuberculosis) and malignancies (including lymphoma).
Additional data presented at ACR showed that patients who withdrew from RAPID 1 and 2 trials because they did not achieve an ACR20 response at Week 12 (confirmed at Week 14) nevertheless showed a slowed progression of structural damage within the joints as measured at Week 16 by analysis of radiographic data.
Additional data presented focused on the effect of treatment with CIMZIA together with MTX in quality of life measurements. In RAPID 1, nearly three-quarters of patients achieved improvements in physical function when treated with CIMZIA together with MTX, including 72.4 percent of those initially treated with CIMZIA 200 mg together with MTX or 70.1 percent of those treated with CIMZIA 400 mg together with MTX.
On a 10-point improvement on the Patients Assessment of Arthritis Pain (PAAP) scale, the data showed an average improvement of 39.1 and 38.1 points for those on CIMZIA 200 mg together with MTX and CIMZIA 400 mg together with MTX, respectively.
"It is exciting to see that these patients are deriving and maintaining improvements on multiple levels with continued CIMZIA treatment," noted Philip Mease, M.D., study investigator at the Seattle Rheumatology Associates and Director of Rheumatology Research at Swedish Medical Center. "Reducing pain and discomfort from RA is extremely important, but it is also noteworthy when patients find treatments that lead to a better overall quality of life."
In RAPID 1, patients treated with CIMZIA together with MTX reported gains in additional work and household work days per month and productive work and household work days per month as early as week 4. Over 6 months, improvements continued compared to the control group. These improvements were maintained for up to one year.
Additionally, data presented shows Health Reported Quality of Life Measurements (HRQoL) approached population norms in the "vitality" and "mental health" domains. As assessed by the Fatigue Assessment Scale of 1 to 10, patients in the trial also reported a mean reduction in fatigue to 3.1 points at week 100 with CIMZIA together with MTX treatment.
Notes to Editors:
RAPID Clinical Trials Program
The international, multi-center, double-blind placebo-controlled RAPID (RA PreventIon of structural Damage) clinical trials were designed to establish the efficacy and tolerability of CIMZIA® (certolizumab pegol) together with methotrexate (MTX) in the treatment of active rheumatoid arthritis who did not adequately respond to conventional treatment. The 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, patients randomly received one of three treatment regimens: 393 patients received CIMZIA 400 mg at weeks 0, 2 and 4, then CIMZIA 200 mg together with MTX every two weeks; 390 patients received CIMZIA 400 mg together with MTX every 2 weeks; 199 patients received placebo together with MTX every 2 weeks. RAPID 1 met co-primary endpoints: ACR20 response rate(a) at week 24 and the change from baseline in mTSS(b) at week 52. An open-label extension study continued to evaluate the effects of CIMZIA over two years.
In the six-month RAPID 2 trial, 619 patients randomly received one of three treatment regimens: 246 patients received CIMZIA 400 mg at weeks O, 2 and 4, then CIMZIA 200 mg together with MTX every two weeks; 246 patients received CIMZIA 400 mg together with MTX every two weeks; 127 patients received placebo together with MTX every two weeks.
In all 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 produced similar clinical results as a dosage of 400mg every two weeks.
(a) ACR (American College 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)
Open-Label Study to RAPID 1 (028)
The Phase III, open-label extension (OLE) study to RAPID 1 is investigating the long-term efficacy and safety of subcutaneous CIMZIA (400 mg every 2 weeks) together with methotrexate in the treatment of signs and symptoms and in the prevention of joint damage in patients with active RA. Patients completing RAPID 1 through 52 weeks (completers), or who were ACR20 nonresponders at Week 12 (confirmed at Week 14) and were to be withdrawn from the study at Week 16 (withdrawers), could continue in the 028 study. The open-label extension study continued to evaluate the effects of CIMZIA over two years.
FAST 4WARD (Study 011)
In the 24-week FAST 4WARD (eFficAcy and Safety of cerTolizumab pegol - 4 Weekly dosAge in RheumatoiD arthritis, Study O11) phase III study, 220 adult patients with active RA who had previously failed at least one disease-modifying antirheumatic drugs (DMARD) were randomized to receive either CIMZIA 400 mg subcutaneously every four weeks (n=111) or placebo (n=109). Patients were assessed for improvement in signs and symptoms of RA. The primary endpoint of the 011 study was ACR20 responder rate, with secondary measures including ACR50 and ACR70 responder rates.
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 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 greater than or equal to 5% 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 (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 North American headquarters is located in Atlanta, Ga.
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.
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