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.
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 gene.
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
biogenidec.
(1) American College of Rheumatology. "Rheumatoid Arthritis.",
rheumatology/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, Inc.
gene
View drug information on Rituxan.
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