Hematology/Oncology 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 second quarter of 2009, we submitted two supplemental Biologics License Applications (sBLA) to the U.S. Food and Drug Administration (FDA), one for previously untreated chronic lymphocytic leukemia and one for relapsed chronic lymphocytic leukemia. The sBLA submissions were granted priority review and have a Prescription Drug User Fee Act (PDUFA) date of November 17, 2009

Phase III clinical trials are ongoing evaluating Rituxan for follicular non-Hodgkin's lymphoma and in combination with Avastin for diffuse large B-cell lymphoma. Clinical trials are also ongoing or planned evaluating Rituxan in combination with investigational targeted agents, such as ABT-263, DR5-Agonist Antibody (PRO95780), dacetuzumab, and dulanermin.

Rituxan is being developed in collaboration with Biogen Idec Inc.

Approved Uses - Hematology/Oncology

• In November 1997, the FDA approved Rituxan for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell, non-Hodgkin's lymphoma as a single agent.
• In April 2001, the FDA approved Rituxan for these additional uses: retreatment of patients with Rituxan who have relapsed following initial Rituxan therapy, use of eight weekly doses (compared to original four) per course of treatment, treatment of patients with bulky disease (lesions > 10 cm).
• In February 2006, the FDA approved Rituxan for the treatment of patients with previously untreated diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy or other anthracycline-based chemotherapy regimens.
• In September 2006, the FDA approved Rituxan for the treatment of patients with previously untreated follicular, CD20-positive, B-cell, non-Hodgkin's lymphoma in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy.
• In September 2006, the FDA approved Rituxan for the treatment of patients with non-progressing (including stable disease), low-grade, CD20-positive, B-cell, non-Hodgkin's lymphoma, as a single agent, after first-line treatment with CVP chemotherapy.

BOXED WARNINGS and Additional 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.

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

September 2009