Saturday, Nov 11, 2006

Subsequent Course of Rituxan Improved Outcomes in Rheumatoid Arthritis Patients Who Inadequately Responded to TNF Antagonist Therapy

Preliminary Safety Data on TNF Antagonist Use Following Rituxan Treatment Also Being Presented at the American College of Rheumatology Meeting

South San Francisco, Calif. and Cambridge, Mass. -- November 11, 2006 --

Genentech, Inc. (NYSE: DNA) and Biogen Idec, Inc. (Nasdaq: BIIB) today announced positive results from interim analyses of ongoing open-label extension studies of Rituxan® (Rituximab) therapy 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. Interim findings showed that a greater proportion of patients achieved an American College of Rheumatology (ACR) 20, 50 or 70 response following treatment with a subsequent course of Rituxan, in combination with methotrexate (MTX), compared to outcomes after their first course. These findings, along with data on physical function and mental and physical health measures and a preliminary safety analysis of TNF antagonist use following Rituxan treatment, are being presented at the ACR Annual Scientific Meeting.

Subsequent Course of Rituxan Treatment: Long-Term Efficacy/Safety Interim Findings
In open-label extension studies that evaluated the long-term efficacy and safety of a subsequent course of Rituxan treatment, 155 patients received Rituxan (1000 mg i.v. infusion on days one and 15) in combination with a stable dose of MTX. Patients treated with a first course of Rituxan in a Phase II or Phase III study were eligible to receive additional open-label treatment courses based on physician discretion if they had active disease (defined as greater than or equal to 8 swollen joint counts and tender joint counts) and a predefined improvement to the first treatment course by week 24 (greater than or equal to 20 percent improvement in joint counts). After 16 weeks or more, patients who received placebo in the original studies were also eligible to enter the extension study and receive one or more courses of Rituxan.

At 24 weeks, following a subsequent course of treatment with Rituxan and MTX, interim study findings showed that patients who responded to a first course of Rituxan treatment also benefited from a subsequent course. Compared to the original baseline:

  • 72 percent (111/155) achieved ACR 20 after a subsequent course, versus 65 percent (101/155) after the first course;
  • 42 percent (65/155) achieved ACR 50 after a subsequent course, versus 33 percent (51/155) after the first course; and,
  • 21 percent (33/155) achieved ACR 70 after a subsequent course, versus 12 percent (19/155) after the first course.

Among all patients in the extension study who received a subsequent course of Rituxan treatment after a previous exposure to at least one TNF antagonist, the rate of serious adverse events (grade 3 or 4) was approximately 11 percent and serious infections occurred in 2 percent of patients. The companies recognize the importance of and will continue to monitor the long-term safety of Rituxan in RA.

"These interim data show that patients who received a subsequent course of Rituxan experienced comparable or improved RA symptom relief compared to outcomes after their first course," said Mark Genovese, M.D., Associate Professor of Medicine, Immunology and Rheumatology, Stanford University Medical Center. The analysis also showed that additional Rituxan treatment in this study was not associated with an increase in infections or adverse events, including infusion reactions."

Subsequent Course of Rituxan Treatment: Physical Function/Physical and Mental Scale Results
A separate analysis of the same studies showed that patients who received a subsequent course of treatment with Rituxan continued to show improvements in physical function and physical and mental health measures, compared to their responses to a first course. According to assessments using the Disability Index of the Health Assessment Questionnaire (HAQ-DI), 69 percent of patients who received a subsequent course of Rituxan treatment experienced a significant improvement in physical function, defined as a decrease in HAQ-DI >0.22, compared with 72 percent of patients after their first course. Additionally, patients who received a subsequent course of Rituxan treatment showed greater mean improvements in mental and physical components of a health-related quality of life questionnaire (Short Form Health Survey) at 24 weeks following the subsequent course of treatment, than after the first course (8.7 versus 4.8 and 7.8 versus 6.4, respectively).

TNF Antagonist Use Following Rituxan Treatment: Preliminary Safety Results
Based on data collected from 78 RA patients who discontinued Rituxan and had peripheral B-cell levels below the lower limit of normal at the time of initiating TNF antagonist therapy (etanercept: 23 patients; infliximab: 23 patients; adalimumab: 25 patients; and more than one TNF antagonist therapy [not concurrently]: seven patients):

  • 14 patients experienced a total of 22 adverse events at the time of the interim analysis. Ten of the adverse events were serious and included RA flare, pleuritic pain, deep vein thrombosis and infections.
  • The number of serious infections was similar in these RA patients during the time they received Rituxan as compared to the time they were taking a TNF antagonist following Rituxan (three versus four, respectively, which corresponded to 0.05 versus 0.08 events per patient year, respectively).
  • The rate of serious infections observed in patients who received TNF antagonist therapy following Rituxan is similar to the rate reported for patients who receive initial treatment only with TNF antagonist therapy.

"These preliminary data are encouraging and we will continue to evaluate this patient group to further understand how patients can be treated following Rituxan therapy," said Mark Genovese, M.D., Stanford University Medical Center.

Rituxan, the first and only therapy for RA that targets CD20-positive B-cells, was approved by the U.S. Food and Drug Administration in February 2006 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.

About ACR Response
ACR 20, ACR 50 and ACR 70 responses indicate a 20, 50 and 70 percent improvement in the number of swollen and tender joints, respectively, as well as a 20, 50 and 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).

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; and,
  • 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 Americans1 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 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, NHL. 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, 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 NHL. It was also approved in the European Union under the trade name MabThera® in June 1998. 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.

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 960,000 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.

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