Chairman and CEO: Franz B. Humer announced today that the humanized anti-human IL-6 receptor monoclonal antibody, Actemra® has shown efficacy as a combination therapy with DMARDs in rheumatoid arthritis patients in a double-blinded phase III trial
TOKYO, Japan | November 8, 2007 | Chugai Pharmaceutical Co., Ltd. [Head Office: Chuo-ku, Tokyo; President Osamu Nagayama (hereinafter, "Chugai")] and F. Hoffmann-La Roche Ltd. (hereinafter "Roche") [Head Office: Basel, Switzerland. Chairman and CEO: Franz B. Humer] announced today that the humanized anti-human IL-6 (interleukin-6) receptor monoclonal antibody, Actemra® (generic name: tocilizumab -genetical recombination- injection), globally co-developed by Chugai and Roche, has shown efficacy as a combination therapy with DMARDs (Disease Modifying Antirheumatic Drugs) in rheumatoid arthritis patients in a double-blinded phase III trial. This is a second phase III trial outside of Japan, and evaluated the efficacy on patients with inadequate response to DMARDs. The results will be presented on November 10, 2007, at the American College of Rheumatology (ACR) Annual Congress held in Boston, USA.
Trial Objective, Design and Results
Objective: To investigate Actemra’s efficacy and safety for rheumatoid arthritis patients with inadequate response to DMARDs treatment.
Method: This is a double-blinded trial evaluating 1,216 patients with moderate to severe active rheumatoid arthritis despite treatment with DMARDs. Patients were allocated to receive Actemra 8mg/kg, or placebo every four weeks (intravenous infusion), in combination with traditional DMARDs.
Results: ACR response rates were used to determine the anti-rheumatic efficacy, and at the end of the 24 weeks (or at the last observation), Actemra group achieved statistically significantly higher response rates versus placebo.
Safety: Actemra was generally well tolerated. The most common adverse events reported more frequently in the Actemra arm were upper respiratory tract infections, headache and nasopharyngitis and hypertension. As with other DMARDs, serious infections have been reported in some patients treated with Actemra.
Actemra® is currently marketed in Japan under the trade name "ACTEMRA® 200 for Intravenous Infusion" after approval as a therapy for Castleman’s disease in April 2005. In April 2006, additional indications were filed in Japan for rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis.
Outside of Japan, Roche and Chugai are investigating Actemra® in five phase III international trials, of which the TOWARD trial is the second to report, following the OPTION trial which was the first to report in June 2007 at European League Against Rheumatism. In those trials, Actemra is being tested in rheumatoid arthritis patients with inadequate response to DMARDs (Disease Modifying Antirheumatic Drugs), including MTX and anti-TNF preparations, and patients who have not been treated with MTX before. Roche plans to file Actemra with regulatory authorities in Europe and in the United States, in the fourth quarter of 2007.
Interleukin-6 (IL-6)
IL-6 was identified as an agent that can induce the differentiation of B cells in immune systems from cells producing antibodies. Later research revealed that IL-6 has diverse physiologic activation properties. They include proliferating and differentiating hematopoietic cells and nerve cells, as well as inflammatory reactions. IL-6 also relates to the pathologies of various immune abnormalities and inflammatory diseases, such as rheumatoid arthritis, Castleman’s disease, Crohn’s disease and multiple myeloma.
Actemra® (humanized anti-human IL-6 receptor monoclonal antibody)
Actemra® is a humanized antibody to the human IL-6 receptor, and was created using genome engineering technology. It controls IL-6 molecules by stopping IL-6 from binding with IL-6 receptors. Actemra® may have applications in the treatment of diseases whose pathologies apparently relate closely to IL-6.
ACR response
The ACR-20 response was developed as one of the measures of improvement in the treatment of rheumatoid arthritis by the American College of Rheumatology, with standards for a 20% response, 50% response and 70% response. An ACR-20 response is defined as a reduction in each patient of at least 20% in criteria (1) and (2) listed below, plus an improvement of at least 20% in at least three of the others.
Disease Activity Measure
(1) Tender joint count
(2) Swollen joint count
(3) Patient’s assessment of pain
(4) Patient’s global assessment of disease
(5) Physician’s global assessment of disease activity
(6) Patient’s assessment of physical function
(7) Acute-phase reactant value
SOURCE: Chugai Pharmaceutical Co., Ltd.
