Investor Update
Basel, 9 June 2005
Preliminary
phase IIb study showed MabThera improved symptoms in rheumatoid arthritis patients who failed one or
more disease-modifying anti-rheumatic drugs
Improvement shown to
be independent of administration of corticosteroids
Roche, Genentech
and Biogen Idec announced today preliminary positive results from a large randomized clinical trial
of MabThera (Rituximab) in rheumatoid arthritis (RA) showing that a greater proportion of patients treated
with a single course of MabThera, with a stable dose of methotrexate (MTX), achieved American College
of Rheumatology (ACR) 20, 50 and 70 response rates compared to placebo. The improvement in response
rates was shown to be independent of corticosteroids. This phase IIb trial included 465 patients who
were inadequately responding to MTX and who had failed prior treatment with one or more disease-modifying
anti-rheumatic drugs (DMARDs), including biologics. Results from this study were presented today at
a leading rheumatology meeting in Vienna, Austria.
The study, known as
DANCER (Dose-Ranging Assessment International Clinical Evaluation of Rituximab in RA), evaluated the
efficacy and safety of two doses of MabThera in combination with MTX and explored the role of corticosteroids.
Patients, randomized into one of nine treatment arms, received a stable dose of MTX and varying doses
of MabThera and corticosteroids. Regardless of dose, the DANCER results indicated that MabThera provided
clinically and statistically significant improvement in RA symptoms compared to placebo. In the two
MabThera groups, 54 percent and 55 percent achieved ACR 20; 33 percent and 34 percent achieved ACR 50;
and 13 percent and 20 percent achieved ACR 70 - compared to 28 percent, 13 percent and 5 percent for
placebo respectively.
“The results of the DANCER study, which evaluated
the efficacy and safety of MabThera in a difficult-to-treat patient population, further validate selective
B-cell depletion as a potentially new and viable approach to the treatment of RA,” said Roy Fleischmann,
M.D., University of Texas Southwestern Medical Center. “For the first time, these data also showed that
the benefits of MabThera were independent of short-course corticosteroids, which were given in all previous
MabThera RA trials.”
The data did not reveal any unexpected safety signals.
The most frequently reported adverse events in the study were primarily infusion-related and mild-to-moderate
in intensity, including headache, nausea and rigors. Intravenous corticosteroid pre-medication appeared
to reduce the incidence and severity of first infusion reactions. Oral corticosteroids did not
appear to provide any additional safety benefit.
The reported rate of
serious adverse events was higher in the MabThera groups, but similar to those seen in previous studies
of MabThera in RA. Across the MabThera groups, 35 percent of patients experienced infections, compared
to 28 percent of placebo patients. However, the type and severity of infections were similar between
both MabThera doses and the placebo regimen. The rate of serious infections was low and was similar
across the treatment groups. In addition, MabThera therapy had no significant impact on immunoglobulin
levels or acquired immunity. The companies are committed to monitoring long-term safety of MabThera
in all clinical trials.
Although there was a trend toward higher ACR
70 responses for patients in one of the MabThera groups, it was not statistically significant. Based
on the DANCER results, the companies are planning to evaluate two doses of MabThera in a phase III study
of patients who are inadequately responding to MTX and who have failed prior treatment with one or more
DMARDs. These phase IIb results follow recent positive findings from a phase III study that evaluated
the efficacy and safety of MabThera in patients with active RA who had an inadequate response or were
intolerant to prior treatment with one or more anti-TNF therapies.
About
the Study
The primary endpoint of DANCER was ACR 20 response at 24 weeks in rheumatoid
factor positive patients (n=367). Both rheumatoid factor positive and rheumatoid factor negative
patients were included in the safety analysis. Of the patients enrolled, 29 percent (134/465) had inadequately
responded to anti-TNF treatments.
About ACR Response
ACR
20, ACR 50 and ACR 70 indicate a 20, 50 or 70 percent improvement in the number of swollen and tender
joints, as well as a 20, 50 or 70 percent improvement compared with baseline in three of five disease-activity
measures: patient assessment, physician assessment, pain scale, Health Assessment Questionnaire and
the value for one acute phase reactant (erythrocyte sedimentation rate or C-reactive protein), respectively.
About
Rheumatoid Arthritis
Rheumatoid arthritis 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.
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 a supplier of innovative products and services for the
early detection, 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 a world leader in diagnostics,
the leading supplier of medicines for cancer and transplantation and a market leader in virology. In
2004 sales by the Pharmaceuticals Division totalled 21.7 billion Swiss francs, while the Diagnostics
Division posted sales of 7.8 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. Additional information about the Roche Group is available on the
Internet (www.roche.com).
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 additional information about the company,
please visit 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 labeling, press
releases and additional information about the company, please visit www.biogenidec.com.