Phase III Study Showed Rituxan Decreased the Progression of Joint Damage in Patients with Early RA

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Phase III Study Showed Rituxan Decreased the Progression of Joint Damage in

Patients with Early Rheumatoid Arthritis (RA)

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From the PharmaLive.com News Archive - Dec. 19, 2008

Phase III Study of Rituxan Plus Methotrexate in Methotrexate-Naïve RA

Patients Met Primary Endpoint --

SOUTH SAN FRANCISCO, Calif. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec 19,

2008 - Genentech, Inc. and Biogen Idec announced today that a Phase III

clinical study of Rituxan (rituximab) in patients with early rheumatoid

arthritis (RA) who have not previously been treated with methotrexate (MTX)

met its primary endpoint.

In this study, known as IMAGE, patients received two infusions of either 500

mg or 1000 mg of Rituxan or placebo for up to two treatment courses in

combination with a stable dose of MTX. At week 52, only patients in the 1000

mg treatment group met the primary endpoint and showed significantly less

progression of joint damage compared to patients who received placebo in

combination with MTX. Joint damage was assessed by changes in X-ray images

using the Genant-modified total Sharp score.

In both Rituxan treatment groups, secondary endpoints showed a significantly

higher proportion of patients with a substantial improvement in RA signs and

symptoms (including ACR scores and DAS remission) compared to patients

receiving MTX alone. Further analyses of the data are ongoing and will be

submitted for presentation at an upcoming medical meeting.

" The study results with Rituxan plus methotrexate in this early RA

population are important because the majority of joint damage -- a leading

cause of disability in patients with RA -- is believed to occur within the

first two years of the disease, often before traditional disease-modifying

drugs like methotrexate have been prescribed, " said Hal Barron, M.D.,

Genentech's senior vice president, Development and chief medical officer.

" The results from IMAGE reinforce our belief that B cells play an important

role in the underlying disease process in RA. "

" The IMAGE study results provide further support for initiating a B-cell

targeted agent earlier in RA treatment, " said Evan Beckman, M.D., Biogen

Idec's senior vice president of Immunology Research and Development.

" The study results also confirm Rituxan's positive impact on disease

activity and physical function in RA patients. We look forward to sharing

the full data set with the medical community and the FDA. "

The safety profile of Rituxan was consistent with our previous experience

and a preliminary analysis did not reveal any new or unexpected safety

signals. The incidence of adverse events and serious adverse events

including infections and serious infections were comparable between Rituxan

and placebo treatment groups. The companies continue to monitor the

long-term safety of Rituxan treatment.

About the IMAGE Study

IMAGE is a multi-year, Phase III, randomized, double-blind,

placebo-controlled, parallel group, multicenter international study designed

to evaluate the safety and efficacy profile of Rituxan in combination with a

stable dose of MTX compared to MTX alone, in methotrexate-naïve patients

with active rheumatoid arthritis.

Methotrexate is a commonly used disease-modifying, anti-rheumatic drug

(DMARD). The primary objective of the study was to determine the efficacy of

Rituxan in the prevention of progression of structural joint damage and to

evaluate the safety of Rituxan in patients with active, early rheumatoid

arthritis initiating treatment with MTX.

A total of 755 MTX-naïve patients with active RA from 168 study sites across

27 countries were randomized to receive either Rituxan (500 mg or 1000 mg)

or placebo by intravenous infusion on days 1 and 15, in addition to therapy

with MTX. Eligible patients who were not in DAS28-ESR remission 24 weeks

following their previous course received a further course of RTX with the

same dose as the first course. The primary endpoint evaluating change in

total Genant-modified total Sharp scores was measured at week 52.

About Rituxan

Rituxan, discovered by Biogen Idec, is a therapeutic antibody that first

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 in June 1998. Rituxan received FDA approval in February 2006 for

the treatment of diffuse large B-cell lymphoma (DLBCL) in combination with

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other

anthracycline-based chemotherapy regimens in previously untreated patients.

In February 2006, Rituxan also received FDA approval in combination with MTX

to reduce 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 January 2008, Rituxan was approved to slow the progression of

structural damage in adult patients with moderately-to-severely active RA

who have had an inadequate response to one or more TNF-antagonist therapies.

Rituxan is the first treatment for RA that selectively targets immune cells

known as CD20-positive B cells. Rituxan does not target the entire immune

system.

CD20 is not found on stem cells, pro-B cells (B cell precursors), normal

plasma cells, or other normal tissues. Rituxan does not target plasma cells.

These cells make antibodies that help fight infections.

Rituxan does not target stem cells in the bone marrow, and B cells can

usually regenerate and gradually return to normal levels after retreatment

with Rituxan in about 12 months for most patients.

In addition, Rituxan received FDA approval in September 2006 for first-line

treatment of previously-untreated patients with follicular NHL in

combination with CVP (cyclophosphamide, vincristine, and prednisolone)

chemotherapy and also for the treatment of low-grade NHL in patients with

stable disease or who achieve a partial or complete response following

first-line treatment with CVP chemotherapy.

Over the past ten years, there have been more than 1 million patient

exposures to Rituxan.

Rituxan is also being studied in other autoimmune diseases with significant

unmet medical needs, including lupus nephritis and antineutrophil

cytoplasmic antibody (ANCA)-associated vasculitis.

Rituxan Safety

Rituxan has been associated with fatal infusion reactions, tumor lysis

syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal

leukoencephalopathy (PML).

Hepatitis B reactivation with fulminant hepatitis, other viral infections,

cardiovascular events, renal toxicity, and bowel obstruction and perforation

have also been observed. Patients should be closely observed for signs of

infection if biologic agents and/or disease modifying anti-rheumatic drugs

(DMARDs) other than methotrexate are used concomitantly.

The most common adverse reactions in Rituxan-treated RA patients are

hypertension, nausea, upper respiratory tract infection, arthralgia,

pruritus, and pyrexia.

The most common adverse reactions in Rituxan-treated NHL patients are

infusion reactions, fevers, chills, infection, asthenia, and lymphopenia.

For additional safety information, please see full prescribing information,

including Boxed Warnings and Medication Guide available at 1-800-821-8590 or

http://www.gene.com