Fourth phase III study with novel interleukin-6 receptor inhibitor meets primary endpoint
BASEL, Switzerland | July 25, 2007 | Roche announced today that AMBITION1, the study aiming to demonstrate the safety and efficacy of Actemra (tocilizumab) monotherapy, successfully met its primary endpoint2 in patients with moderate to severe rheumatoid arthritis (RA). This is the fourth study in Actemra’s extensive multinational phase III development programme. The study examined the use of Actemra monotherapy against a standard, effective regimen of methotrexate in patients with active RA, including a high proportion of patients with early disease. The data show that a greater proportion of patients treated with Actemra (8mg/kg), achieved a significant improvement in disease signs and symptoms (ACR scores3) following 24 weeks of treatment, compared to patients treated with methotrexate alone.
"This is the first multinational phase III trial using Actemra monotherapy. The trial demonstrates Actemra’s safety and efficacy, reinforcing the role of IL-6 receptor inhibition in RA" said William M. Burns, CEO Pharmaceuticals Division of Roche. "These exciting data support Actemra’s potential as a new future therapy for RA patients."
The study, together with data from the previous three international studies, will form the basis of the regulatory filing for marketing approval later this year.
About the AMBITION study
The AMBITION trial is a two-arm, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of Actemra (8 mg/kg) compared to methotrexate in RA patients. Patients received either Actemra intravenously (8 mg/kg) every four weeks plus placebo capsules weekly or placebo infusions every four weeks plus methotrexate weekly. The study included 673 patients at 252 trial sites in 18 countries, including the United States.
Previous and ongoing studies
The AMBITION trial is one of five phase III clinical studies designed to evaluate Actemra as a potential new treatment for RA. Three of the phase III trials – OPTION4, TOWARD5 and RADIATE6 – are completed and have reported meeting their primary study endpoints. At the European Congress of Rheumatology meeting in June, data results from the OPTION trial demonstrated that treatment with Actemra plus methotrexate resulted in a significant improvement in RA symptoms in patients who had an inadequate response to methotrexate. An additional phase III trial evaluating Actemra in RA is ongoing; the two-year study, called LITHE, is expected to report later in 2008. Data from the AMBITION study will be submitted for presentation at future international scientific meetings.
About Actemra
Actemra is the first humanised interleukin-6 (IL-6) receptor inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA, a disease with a high unmet medical need. The overall safety profile observed in the global studies of Actemra is consistent and Actemra is generally well tolerated. The most frequent adverse events reported have included upper respiratory tract infections, headache, nasopharyngitis and hypertension. As with other biological disease modifying anti-rheumatic drugs (DMARDs), serious infections have been reported in some patients treated with Actemra.
Roche and Chugai are collaborating on a phase III clinical development programme in RA running outside Japan, with more than 4000 patients enrolled in 41 countries including several European countries and the USA. In Japan, Actemra was launched in June 2005 as a therapy for Castleman’s disease and in April 2006 filed for the additional indications of rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis.
About rheumatoid arthritis
Rheumatoid arthritis is a progressive, systemic autoimmune disease characterized by chronic inflammation of multiple joints and fatigue as well as the possibility of osteoporosis, anaemia, and lung, skin and liver effects. This inflammation causes pain, stiffness and swelling, resulting in loss of joint function due to destruction of the bone and cartilage, often leading to progressive disability. Further, as chronic inflammation continues, there may be shortening of life expectancy as a result of effects on major organ systems. After 10 years, less than 50% of patients can continue to work or function normally on a day to day basis. RA affects more than 21 million people worldwide.
About Roche in rheumatoid arthritis
One of the most important drivers for growth at Roche over the next few years is expected to be the company’s emerging franchise in autoimmune diseases with rheumatoid arthritis as the first indication. Following the launch of MabThera® (rituximab) there are a number of projects in development, potentially allowing Roche to build on further opportunities. MabThera is the first and only selective B-cell therapy for RA, providing a fundamentally different treatment approach by targeting B cells, one of the key players in the pathogenesis of RA. Actemra is Roche’s second novel medicine and is a humanised monoclonal antibody to the interleukin-6 (IL-6) receptor, inhibiting the activity of IL-6 , a protein that plays a major role in the RA inflammation process. Actemra is the result of research collaboration by Chugai and is being co-developed globally with Chugai. Additional projects creating a rich pipeline include compounds in Phase I, II and III clinical trials. Notably, ocrelizumab, a humanised anti-CD20 antibody, has entered phase III development for RA.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs approximately 75,000 worldwide and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet at www.roche.com.
References
1) AMBITION refers to Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy trial
2) The proportion of patients who achieved ACR20 at week 24
3) The ACR response is a standard assessment used to measure patients’ responses to anti-rheumatic therapies, devised by the American College of Rheumatology (ACR). It requires a patient to have a defined percentage reduction in a number of symptoms and measures of their disease. For example, a 20%, 50% or 70% level of reduction (the percentage of reduction of RA symptoms) is represented as ACR20, ACR50 or ACR70. An ACR70 response is exceptional for existing treatments and represents a significant improvement in a patient’s condition.
4) OPTION refers to the TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders
5) TOWARD refers to Tocilizumab in cOmbination With traditional DMARD therapy
6) RADIATE refers to Research on Actemra Determining effIcacy after Anti-Tnf FailurEs
SOURCE: Roche
