Analysis of Phase III Study Showed Rituxan(R) Plus Methotrexate ...
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inflammation, often ... of the joints, swelling, fatigue, stiffness and
... acute respiratory distress syndrome, myocardial infarction ...
Analysis of Phase III Study Showed Rituxan(R) Plus Methotrexate Reduced
Joint Damage in Rheumatoid Arthritis Patients Who Respond Inadequately
to TNF Antagonist Therapies
June 22, 2006 - 9:59 AM
Findings on Mean Change in Genant-Modified Sharp Score in Patients With
Moderate-to-Severe RA Presented at Leading Rheumatology Meeting
SOUTH SAN FRANCISCO, Calif. and CAMBRIDGE, Mass., June 22
/PRNewswire-FirstCall/ -- Genentech, Inc. (NYSE:DNA) and Biogen Idec,
Inc. (NASDAQ:BIIB) today announced positive results from an analysis of
REFLEX, a Phase III clinical study of Rituxan(R) (Rituximab) in
patients with rheumatoid arthritis (RA) who have had an inadequate
response to previous treatment with one or more tumor necrosis factor
(TNF) antagonist therapies. The findings showed that treatment with
Rituxan in combination with a stable dose of methotrexate (MTX) reduced
joint erosion and joint space narrowing at 56 weeks, compared to
placebo and MTX. These are the first data to measure the progression of
joint damage in this difficult-to-treat patient population. Results
were presented for the first time today at a rheumatology meeting in
Amsterdam, Netherlands.
Rituxan, the first and only CD20-positive B-cell-targeted therapy for
RA, was recently approved by the U.S. Food and Drug Administration for
use in combination with MTX for reducing signs and symptoms in adult
patients with moderately-to-severely active RA who have had an
inadequate response to one or more TNF antagonist therapies.
In this analysis at 56 weeks, patients treated with Rituxan and MTX
displayed the following improvements, compared to patients who received
placebo and MTX:
-- The mean change in the composite Genant-modified Sharp score, which
assesses progression of both joint erosion and joint space narrowing,
was lower among Rituxan-treated patients than placebo-treated patients
(1.00 versus 2.31, respectively; p = 0.0046).
-- Mean changes in the erosion score (0.59 versus 1.32; p = 0.0114) and
joint space narrowing score (0.41 versus 0.99; p = 0.0006) were lower
among Rituxan-treated patients than placebo-treated patients.
-- A higher proportion of Rituxan-treated patients showed no additional
erosion, compared to patients who received placebo (61 percent versus
52 percent, respectively; p = 0.0445).
"These data suggest that even the most difficult-to-treat RA patients
who have not responded to prior TNF therapy may be able to reduce joint
erosion and narrowing following treatment with Rituxan and
methotrexate," said Edward Keystone, M.D., University of Toronto,
Canada. "Considering joint destruction leads to deformity and
disability, it is imperative to continue researching potential
approaches to address this debilitating process."
In the multi-center, double-blind, placebo-controlled REFLEX study,
patients were randomized to receive either a single treatment course of
two infusions of Rituxan (1000 mg on days one and 15) or placebo, in
combination with a stable dose of MTX and followed through 24 weeks.
Following week 24, patients with active RA that had either demonstrated
a response to an initial treatment course of Rituxan or had initially
received placebo, were eligible for a subsequent or initial course of
Rituxan treatment, respectively, and were followed through 56 weeks.
X-rays of the hands and feet were taken at the start of the study and
at weeks 24 and 56, and assessed using the Genant-modified Sharp
method. Of the 520 total patients in the study, this analysis evaluated
X-rays from 277 of the 311 Rituxan-treated patients and 186 of the 209
placebo-treated patients.
In the primary REFLEX study, the most frequently reported adverse
events that occurred with Rituxan through 24 weeks were primarily
infusion- associated. Serious adverse events occurred in 7 percent of
patients receiving Rituxan and MTX compared to 10 percent in patients
receiving placebo and MTX. Less than 1 percent of acute infusion
reactions were serious. The incidence of serious infections was 2
percent in Rituxan-treated patients and 1 percent in placebo-treated
patients. The companies are committed to monitoring long-term safety of
Rituxan.
About Radiographic Analysis of Joint Structural Damage
Data on the progression of joint structural damage are obtained by
taking X-rays of specific joints (typically in the hands and feet)
before treatment and at various points after treatment has been
initiated. The Genant-modified Sharp method focuses on 14 specific
sites for evidence of bone erosion and 13 sites for narrowing of the
joint space -- both key measures of ongoing structural damage to the
joints. Erosion scores are assigned to each of the specified sites,
with 0 representing "no erosion" and 3.5 representing "destruction of
the joint." Joint space narrowing scores are assigned to each of the
specified sites, with 0 representing "no narrowing" and 4 representing
"total loss of the joint space." Increases in the scores indicate the
extent of additional erosion, joint space narrowing or overall
structural damage (both scores combined) that have occurred since
treatment began.
About the Role of B-cells in Rheumatoid Arthritis
While RA has traditionally been considered a T-cell-mediated disease,
newer research suggests that other immune cells called B-cells may play
multiple roles in the initiation and development of RA, including:
-- Presentation of antigens (substances capable of triggering an immune
response), which may contribute significantly to T-cell responses
-- Production of antibodies that trigger an immune attack against a
person's own cells or tissues (autoantibodies) and perpetuate the
disease process
-- Production of chemical signal molecules (cytokines) known to promote
inflammation and joint damage
About RA
RA is a debilitating autoimmune disease that affects more than two
million Americans(1) and hinders the daily activities of sufferers. The
damage that occurs in RA is a result of the immune system attacking
joint tissue, causing painful chronic inflammation, often resulting in
irreversible destruction of cartilage, tendons and bones, often
resulting in disability. 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 and eyes.
Rituxan Safety Profile
In general, the adverse events observed in patients with RA were
similar in type to those seen in patients with non-Hodgkin's lymphoma
(NHL).
The most common adverse events observed in patients treated with
Rituxan for RA in clinical trials were infusion reactions and
infections. No significant change in average immunoglobulin levels was
observed in Rituxan- treated patients in clinical trials. There was no
increase in hematologic malignancies, demyelinating events or risk of
opportunistic infections (including tuberculosis) in Rituxan-treated
patients over 24 weeks of treatment. Although 5 percent of
Rituxan-treated RA patients developed human anti-chimeric antibodies
(HACA), this was not associated with loss of clinical response or
additional safety observations.
The majority of patients experiencing an infusion-related reaction will
do so during their first Rituxan infusion. These symptoms include but
are not limited to: flu-like illness, fever, chills/rigors, nausea,
urticaria, headache, bronchospasm, angioedema, hypotension and hypoxia.
These symptoms vary in severity and generally are reversible with
medical intervention.
Severe infusion reactions have been reported in patients treated with
Rituxan, some with fatal outcomes in patients with NHL. These severe
reactions typically occur during the first infusion. The most severe
manifestations and sequelae include pulmonary infiltrates, acute
respiratory distress syndrome, myocardial infarction, ventricular
fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid
events. Patients who develop clinically significant infusion reactions
should have their Rituxan infusion discontinued and receive medical
treatment. Acute renal failure requiring dialysis with instances of
fatal outcome has been reported in the setting of tumor lysis syndrome
following treatment with Rituxan.
Severe mucocutaneous skin reactions, some with fatal outcome, have been
reported in association with Rituxan treatment. Patients experiencing a
severe mucocutaneous reaction should not receive any further infusions
and seek prompt medical evaluation. Abdominal pain, bowel obstruction
and perforation, in some cases leading to death, were observed in
patients receiving Rituxan in combination with chemotherapy for diffuse
large B-cell (DLBCL), CD20-positive, non-Hodgkin's lymphoma. Other
serious or potentially life-threatening adverse reactions that have
been reported following Rituxan therapy include Hepatitis B
reactivation with fulminant hepatitis, other viral infections,
hypersensitivity reactions, and cardiac arrhythmias.
About Rituxan
Rituxan is a therapeutic antibody that targets and selectively depletes
CD20-positive B-cells without targeting stem cells or existing plasma
cells. In RA patients who respond inadequately to TNF antagonist
therapy, Rituxan is given as two 1000 mg IV infusions separated by two
weeks, in combination with MTX. It is recommended to administer the
steroid methylprednisolone 100 mg IV 30 minutes prior to each infusion.
In addition to RA, Rituxan is being studied in other autoimmune
diseases with significant unmet medical needs, including systemic lupus
erythematosus, lupus nephritis, multiple sclerosis and ANCA-associated
vasculitis.
Rituxan, discovered by Biogen Idec, received FDA approval in November
1997 for the treatment of relapsed or refractory, low-grade or
follicular, CD20-positive, B-cell non-Hodgkin's lymphoma. It was also
approved in the European Union under the trade name MabThera(R) in June
1998. In addition, Rituxan received FDA approval in February 2006 for
the treatment of DLBCL in combination with CHOP (cyclophosphamide,
doxorubicin, vincristine and prednisone) or other anthracycline-based
chemotherapy regimens in previously untreated patients. On March 30,
2006, the companies also announced the submission of a sBLA to the FDA
for the use of Rituxan, for the first-line treatment of patients
(previously untreated) with low-grade or follicular, CD20-positive,
B-cell non-Hodgkin's lymphoma in combination with CVP
(cyclophosphamide, vincristine and prednisone) or CHOP chemotherapy or
following CVP chemotherapy for patients who achieved a response of
stable disease or better.
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 by Chugai and Zenyaku Kogyo Co. Ltd. Rituxan is
the top-selling oncology therapeutic in the United States with more
than 730,000 patient exposures 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/.
About Genentech
Founded 30 years ago, 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 and licenses several additional
products to other companies. The company has headquarters in South San
Francisco, California and is listed 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, neurology 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/.
(1) American College of Rheumatology. "Rheumatoid Arthritis.",
http://www.rheumatology.org/public/factsheets/ra_new.asp?aud=pat,
accessed 1/13/06.
The statement made in this press release relating to the potential of
Rituxan plus methotrexate to reduce joint erosion and narrowing is
forward-looking. Such statement is a prediction and involves risks and
uncertainties such that the actual result may differ materially. Among
other things, Rituxan as a potential treatment could be affected by
unexpected safety, efficacy or manufacturing issues, the need for
additional clinical studies, additional time requirements for data
analysis, sBLA preparation or decision-making, FDA actions or delays,
failure to receive FDA approval, competition, reimbursement, pricing,
the ability to supply product or a product withdrawal. Please also
refer to Genentech's and Biogen Idec's periodic reports filed with the
Securities and Exchange Commission. Genentech and Biogen Idec disclaim,
and do not undertake, any obligation to update or revise the
forward-looking statement in this press release.
Genentech Contacts:
Media: Nikki Levy (650) 225-1729
Investor: Susan Morris (650) 225-6523
Biogen Idec Contacts:
Media: Amy Ryan (617) 914-6524
Investor: Elizabeth Woo (617) 679-2812
Source: Genentech, Inc.
CONTACT: media, Nikki Levy, +1-650-225-1729, or investors, Susan
Morris,
+1-650-225-6523, both of Genentech, Inc.; or media, Amy Ryan,
+1-617-914-6524,
or investors, Elizabeth Woo, +1-617-679-2812, both of Biogen Idec, Inc.
Web site: http://www.gene.com/
http://www.biogenidec.com/
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