Preliminary Phase IIb Study Showed Rituxan Improved Symptoms in Rheumatoid Arthritis Patients Who Failed One or More Disease-Mod
09 Juin 2005 - 1:00PM
PR Newswire (US)
Preliminary Phase IIb Study Showed Rituxan 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 VIENNA, Austria,
June 9 /PRNewswire-FirstCall/ -- Genentech, Inc. (NYSE: DNA),
Biogen Idec (NASDAQ:BIIB) and Roche (SWX Zurich) announced today
preliminary positive results from a large randomized clinical trial
of Rituxan(R) (Rituximab) in rheumatoid arthritis (RA) showing that
a greater proportion of patients treated with a single course of
Rituxan, 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 Rituxan 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 Rituxan and
corticosteroids. Regardless of dose, the DANCER results indicated
that Rituxan provided clinically and statistically significant
improvement in RA symptoms compared to placebo. In the two Rituxan
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 Rituxan 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 Rituxan were independent of
short-course corticosteroids, which were given in all previous
Rituxan 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 Rituxan groups, but similar to
those seen in previous studies of Rituxan in RA. Across the Rituxan
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 Rituxan doses and the placebo
regimen. The rate of serious infections was low and was similar
across the treatment groups. In addition, Rituxan therapy had no
significant impact on immunoglobulin levels or acquired immunity.
The companies are committed to monitoring long-term safety of
Rituxan in all clinical trials. Although there was a trend toward
higher ACR 70 responses for patients in one of the Rituxan groups,
it was not statistically significant. Based on the DANCER results,
the companies are planning to evaluate two doses of Rituxan 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 Rituxan 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 RA RA is a debilitating autoimmune disease that
affects more than two million Americans(1) and hinders the daily
activities of sufferers. RA occurs when the immune system
inappropriately attacks joint tissue, causing chronic inflammation
and irreversible destruction of cartilage, tendons and bones, often
resulting in disability. While RA has traditionally been considered
a T-cell-mediated disease, emerging research suggests that other
immune cells called B cells may play multiple roles in the
pathophysiology of RA including autoantibody production, T-cell
activation and cytokine production. Common RA symptoms include
inflammation of the joints, swelling, fatigue, stiffness and pain.
Additionally, since RA is a systemic disease, it can have effects
in other tissues such as the lungs, eyes and bone marrow. About
Rituxan Rituxan is a therapeutic antibody that targets and
selectively depletes CD20 positive B cells without targeting stem
cells or existing plasma cells. B cells may play multiple roles in
the pathophysiology of RA. Rituxan is also being investigated in
other autoimmune diseases, including lupus, multiple sclerosis and
ANCA-associated vasculitis. Rituxan received U.S. Food and Drug
Administration approval in November 1997 for the treatment of
relapsed or refractory low-grade or follicular, CD20 positive, B
cell non-Hodgkin's lymphoma (NHL). It also was approved in the
European Union under the trade name MabThera(R) in June 1998.
Genentech and Biogen Idec co-market Rituxan in the United States,
and Roche markets MabThera in the rest of the world, except Japan,
where Rituxan is co-marketed with Zenyaku Kogyo Co. Ltd. Rituxan
has been used to treat more than 500,000 patients worldwide. For a
copy of the Rituxan full prescribing information, including Boxed
Warning, please call 1-800-821-8590 or visit http://www.gene.com/ .
Rituxan Safety Profile in NHL In NHL patients, the majority of
patients experience infusion-related symptoms with their first
Rituxan infusion. These symptoms include but are not limited to:
flu-like fever, chills/rigors, nausea, urticaria, headache,
bronchospasm, angioedema and hypotension. These symptoms vary in
severity and generally are reversible with medical intervention. In
rare instances, severe and fatal infusion-related reactions have
occurred, nearly all of which have been associated with the first
Rituxan infusion. These events appear as manifestations of an
infusion-related complex and include hypoxia, pulmonary
infiltrates, acute respiratory distress syndrome, myocardial
infarction, ventricular fibrillation, cardiogenic shock and tumor
lysis syndrome. Patients who develop clinically significant
infusion-related cardiopulmonary events should have their Rituxan
infusion discontinued and receive medical treatment. In rare
instances, severe mucocutaneous skin reactions have occurred that
may be associated with Rituxan therapy. Many of these reactions
have been described as paraneoplastic pemphigus and are known to be
associated with various B cell lymphomas, particularly NHL and
chronic lymphocytic leukemia. Patients who develop a severe
mucocutaneous skin reaction should have Rituxan discontinued and
receive appropriate medical treatment, including a skin biopsy to
guide therapy. 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 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 labeling, press releases
and additional information about the company, please visit
http://www.biogenidec.com/. 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 totaled 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. (1)
American College of Rheumatology, 2005,
http://www.rheumatology.org/public/factsheets/ra.asp?aud=pat
Genentech Contacts: Media: Ed Lang (650) 467-8606 Investor: Kathee
Littrell (650) 225-1034 Biogen Idec Contacts: Media: Amy Ryan (617)
914-6524 Investor: Elizabeth Woo (617) 679-2812 Roche Contact:
Media Office +41 61 68 88888 DATASOURCE: Genentech, Inc. CONTACT:
Media - Ed Lang, +1-650-467-8606, or Investor - Kathee Littrell,
+1-650-225-1034, both of Genentech; or Media - Amy Ryan,
+1-617-914-6524, or Investor - Elizabeth Woo, +1-617-679-2812, both
of Biogen Idec; or Roche Media Office, +41 61 68 88888 Web site:
http://www.biogenidec.com/ Web site: http://www.gene.com/
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