MabThera for moderate-severe rheumatoid arthritis, good study results

Main Category: Arthritis / Rheumatology
Article Date: 02 Nov 2004 - 12:00 PDT


Roche together with development partners Genentech and Biogen Idec announced today that a Phase IIb clinical study of MabThera/Rituxan (rituximab) met its primary endpoint of a greater proportion of MabThera-treated patients achieving an American College of Rheumatology (ACR) 20 response at week 24, compared to placebo, in patients who were also treated with methotrexate (MTX). In this study, patients with moderate-to-severe rheumatoid arthritis (RA) who received two infusions of MabThera over a two-week period in combination with a stable dose of MTX experienced improved symptoms compared to patients who received placebo and MTX. The benefit in the MabThera/Rituxan treated patients was present regardless of whether additional corticosteroids were administered.

"The preliminary data from this latest study in rheumatoid arthritis confirms MabThera as a promising alternative to current therapies available to patients with RA and are consistent with earlier data showing efficacy and safety of MabThera. As we continue to explore and evaluate MabThera as a potential treatment for RA, we look forward to the results of ongoing analyses which will be presented next year", commented Dr. Eduard Holdener, Head of Global Pharma Development, Roche.

This Phase IIb study, DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of Rituximab in RA), was designed to evaluate the efficacy and safety of varying doses of MabThera/Rituxan in combination with methotrexate in patients with active RA who currently have an inadequate response to methotrexate. The influence of a short initial course of corticosteroids was also evaluated.

All regimens in the study were generally well tolerated. The reported rate of serious adverse events was not significantly different than seen in previous studies of MabThera/Rituxan in RA. MabThera/Rituxan is also being studied in an additional ongoing trial, REFLEX (Randomised Evaluation oF Long-term Efficacy rituXimab in RA) in patients who have an inadequate response to anti-TNF alpha (tumour necrosis factor) therapies.

MabThera/Rituxan is a therapeutic antibody that selectively depletes B cells, which may play a key role in the inflammatory cascade of RA. B cells are an important element in the immune system, helping the body to fight off infection. However in autoimmune diseases like RA, the immune system acts abnormally leading to an attack on normal healthy tissue such as the joints.

By depleting B cells, which are believed to be involved in maintaining the attack on healthy tissue, MabThera/Rituxan is thought to break the cycle of rheumatoid arthritis disease. MabThera/Rituxan is already proven effective in RA following a single course of therapy1,2.

There is a large unmet clinical need for RA treatments. Only around 50 percent of patients respond to and maintain treatment with DMARD (disease modifying anti-rheumatic drugs) therapy long term. Data from existing clinical trials indicates that MabThera/Rituxan is safe and well-tolerated in people with RA.

About the Study

DANCER (Dose-Ranging Assessment iNternational Clinical Evaluation of R in RA) is a Phase IIb study evaluating the efficacy and safety of varying doses of MabThera/Rituxan and corticosteroids in combination with a fixed dose of methotrexate in patients who have failed at least one disease-modifying anti-rheumatic drug (DMARD) and are inadequately responding to methotrexate. A total of 465 patients from the United States, Canada, Europe, and Australia were randomised in this multi-centre, randomised, double-blind, placebo-controlled study. DANCER included three different dosages of MabThera/Rituxan (placebo; 2x500mg; 2x1000mg) and corticosteroid (placebo; i.v. 200mg; and i.v. 200mg + p.o. 570mg).

About MabThera/Rituxan

Unlike current RA treatments, MabThera/Rituxan is a therapeutic monoclonal antibody that selectively targets B cells, which are believed to play a key role in the inflammatory cascade of the disease. By doing so, MabThera/Rituxan aims to break the inflammatory cascade of RA - a series of reactions inflaming the synovia and leading to the cartilage loss and bone erosion that is characteristic of the disease in which B cells are thought to play a key role. MabThera/Rituxan has been used for over 7 years for the treatment of a form of lymphatic cancer called non-Hodgkin's lymphoma (NHL) with over 380,000 patients treated to date.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease characterized by inflammation of the membrane lining in joints. This inflammation causes a loss of joint shape and function, resulting in pain, stiffness and swelling, ultimately leading to irreversible joint destruction and disability. Characteristics of RA include redness, swelling, pain, and movement limitation around joints of the hands, feet, elbows, knees and neck. In more severe cases of RA the eyes, lungs or blood vessels may be involved. RA may also shorten life expectancy by affecting major organ systems and after 10 years, less than 50% of patients can continue to work or function normally on a day to day basis. RA is one of the most common forms of autoimmune disease and affects more than 6 million people worldwide, up to 2 million of whom are in Europe.

ACR improvements

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 or 50 percent level of reduction (the percentage of reduction of RA symptoms) is represented as ACR20, ACR50. ACR 20 indicates a 20 percent improvement in the number of swollen and tender joints, as well as a 20 percent improvement in three of five categories: patient assessment, physician assessment, pain scale, Health Assessment Questionnaire, and acute phase reactant (erythrocyte sedimentation rate or c-reactive protein) ACR50 response is exceptional for existing treatments and represents a significant improvement in a patient's condition. A 'Major Clinical Response' is defined as a continuous ACR 70 maintained for at least 6 months.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is number one in the global diagnostics market, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

About Genentech

Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the United States and licenses several additional products to other companies. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional information about the company, please visit http://www.gene.com.

About Biogen Idec

Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing, and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare. For product labelling, press releases and additional information about the company, please visit http://www.biogenidec.com.

All trademarks used or mentioned in this release are legally protected.

References:

1. Edwards J et al. Efficacy of B-cell targeted therapy with rituximab in patients with rheumatoid arthritis. New England Journal of Medicine 2004;350:2572-81
2. Emery P et al. Efficacy and safety of rituximab at 2 years following a single treatment in patients with active arthritis. Oral presentation ACR 2004.

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