Immunology Description Rituxan® (rituximab), discovered by Biogen Idec, is a therapeutic antibody, which binds to the CD20 antigen on the surface of normal and malignant B-cells. From there, it recruits the body's natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.

Development Status In the third quarter of 2008, we submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the potential treatment of rheumatoid arthritis patients who have had an inadequate response to disease modifying anti-rheumatic therapies, or DMARDs. This submission has a Prescription Drug User Fee Act (PDUFA) date of October 16, 2009.

Data results from the Phase III clinical trial in ANCA-associated vasculitis (known as RAVE) will be presented at the American College of Rheumatology, October 16-21, 2009, in Philadelphia.

Rituxan is being developed in collaboration with Biogen Idec Inc.

Approved Uses - Immunology

• In February 2006, the FDA approved Rituxan in combination with methotrexate to reduce signs and symptoms in adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.
• In January 2008, the FDA approved Rituxan in combination with methotrexate for slowing the progression of structural damage in adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.

BOXED WARNINGS and Important Safety Information Patients treated with Rituxan may experience serious or life-threatening side effects, including:

• Progressive Multifocal Leukoencephalopathy (PML, a rare condition that causes nerve damage within the brain)
• Fatal infusion reactions
• Tumor Lysis Syndrome (TLS)
• Severe skin reactions

Other serious and life-threatening side effects include: hepatitis B virus infections with related serious liver problems, other viral infections, heart problems, kidney failure, and stomach and bowel problems.

Common side effects during Rituxan infusions include: fever, headache, chills and shakes, nausea, itching, hives, cough, sneezing, and throat irritation or tightness. These usually occur within 24 hours after the first infusion.

Other common side effects include headache, nausea, upper respiratory tract infection, and aching joints.

For Rituxan full prescribing information, including Boxed WARNINGS, Medication Guide and additional important safety information, please visit http://www.rituxan.com or call 1-800-821-8590.

Additional Information on Clinical Trials For inquiries about our clinical trials, please submit a request through our information request form or call (888) 662-6728.

National Institutes of Health Website: www.clinicaltrials.gov

October 2009