Rituxan® (Rituximab)

Full Prescribing Information, including Boxed WARNINGS and Medication Guide

Date	Event
1975		Therapeutic antibodies are developed by scientists Cesar Milstein and Georges Kohler
1976		Genentech is founded, marking the birth of the biotech industry
1984		Magic Bullets, a book about the use of therapeutic antibodies being used to treat cancer, is published
1984		Milstein and Kohler win the Nobel Prize
1995		Genentech and IDEC sign collaboration to develop and commercialize Rituxan
1996		Pivotal Phase III data on Rituxan is presented at the American Society of Hematology (ASH) meeting
1997		The FDA approves Rituxan, the first therapeutic antibody approved for the treatment of cancer (relapsed or refractory, CD20+, B-cell low-grade non-Hodgkin's lymphoma) Rituxan can cause serious side effects, including: Progressive Multifocal Leukoencephalopathy (PML), which is a rare brain infection. PML usually causes death or severe disability. PML usually happens in patients with weakened immune systems. PML can occur during treatment with Rituxan or after treatment has finished. There is no known treatment, prevention, or cure for PML. Infusion reactions: Patients may get hives, swelling, dizziness, blurred vision, drowsiness, headache, cough, wheezing, or have trouble breathing while receiving or after receiving Rituxan. Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of certain types of cancer cells. TLS can cause kidney failure and the need for dialysis treatment. Severe skin reactions: Patients may get painful sores on the skin or in the mouth, ulcers, blisters, or peeling skin while receiving or after receiving Rituxan.
1998		Rituxan is approved in the European Union under the trade name MabThera®
2001		A supplemental Biological License Application (sBLA) is approved by the FDA for Rituxan adding several new uses, including: Retreatment of patients with Rituxan who have relapsed following initial Rituxan therapy Use of eight weekly doses per course of treatment Treatment of patients with bulky disease (lesions >10 cm)
2002		New England Journal of Medicine publishes data from the Phase III GELA study demonstrating that Rituxan plus CHOP chemotherapy may offer previously-untreated patients the potential for a significant improvement in event-free and overall survival compared to CHOP alone – represents the first improvement in survival in this patient population in more than 25 years The most common side effects of Rituxan in patients with non-Hodgkin's lymphoma (NHL) include: infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common serious side effect in NHL patients was low white blood cells.
2002		Data from studies featuring Rituxan in the treatment of rheumatoid arthritis is presented at the American College of Rheumatology (ACR) annual meeting
2002		More than 190 abstracts on Rituxan presented at the ASH annual meeting
2003		Biogen, Inc. and IDEC Pharmaceuticals Corporation merge to form Biogen Idec Inc.
2003		More than 200 abstracts presented at ASH
2004		More than 250 abstracts presented at ASH
		New England Journal of Medicine publishes the results of a Phase IIa study of Rituxan in patients with moderate-to-severe rheumatoid arthritis (RA)
		DANCER, a Phase IIb study of Rituxan in RA, met its primary endpoint
2005		REFLEX, a Phase III clinical study of Rituxan in RA, met its primary endpoint
2006		On February 10, 2006 Rituxan is approved for the first-line treatment of patients with diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens.
		On February 28, 2006 Rituxan is approved in combination with methotrexate (MTX) to reduce signs and symptoms in adult patients with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.*
		On September 29, 2006 Rituxan is approved for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (NHL) as a single agent; for previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy regimens; for previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy; and for the treatment of non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent, after first-line CVP chemotherapy. WARNINGS Rituxan can cause serious side effects that can lead to death, including: Infusion Reactions: Serious infusion reactions can happen during the infusion or within 24 hours of receiving Rituxan. Patients must tell their doctor or get medical help right away if they get any of these symptoms: hives (itchy red welts) or rash, itching, swelling of the lips, tongue, throat, or face, sudden cough, shortness of breath, difficulty breathing or wheezing, weakness, dizziness or feel faint, palpitations (feel like your heart is racing or fluttering) chest pain. Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus. People with a weakened immune system can get PML. PML can result in death or severe disability. Patients must tell their doctor right away if they have any of the following symptoms: confusion or problems thinking, loss of balance, change in the way they walk or talk, decreased strength or weakness on one side of their body, blurred vision or loss of vision. Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells and can occur after treatment with Rituxan. TLS can cause a person to have kidney failure and the need for dialysis treatment. TLS may also cause abnormal heart rhythm. Severe Skin and Mouth Reactions: Patients may get painful sores on the skin or in the mouth, ulcers, blisters, or peeling skin while receiving or after receiving Rituxan. Rituxan has also been associated with serious and life-threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel that can sometimes lead to death. Common side effects during Rituxan infusions include: fever, headache, chills and shakes, nausea, itching, hives, cough, sneezing, and throat irritation or tightness.
2008		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.* Common side effects include infections and infusion reactions. Before treatment with Rituxan, patients should tell their doctor if they have an infection, including one that will not go away or keeps coming back. If patients experience any symptoms or side effects during or after Rituxan treatment, they should seek immediate medical attention.
2010		In February 2010, the FDA approved Rituxan in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL). The most common side effects of Rituxan seen in clinical trials of patients with CLL were infusion reactions and low white blood cells, which can increase the risk of infections. Patients should talk to their doctor about their medical history before starting treatment with Rituxan.

* The RA indication was revised in October 2009 in conjunction with updated label as follows: Rituxan® (Rituximab) is indicated for use in combination with methotrexate for the treatment of adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

People with serious infections should not receive Rituxan.

Important Safety Information

• Rituxan can cause serious side effects that can lead to death, including: infusion reactions, tumor lysis syndrome (kidney failure due to fast breakdown of cancer cells), severe skin and mouth reactions, and progressive multifocal leukoencephalopathy (a rare, serious brain infection).
• Rituxan has also been associated with serious and life-threatening side effects, including: the return of active hepatitis B virus infection with sudden and serious liver problems including liver failure, and death, other serious infections that can lead to death, heart problems, kidney problems, and stomach and serious bowel problems including blockage and tears in the bowel, that can sometimes lead to death.
• Other serious, potentially life-threatening side effects seen in RA patients are: hepatitis B infection that may become active again, other infections, heart problems, and low blood cell counts.
• The most common side effects of Rituxan seen in patients with non-Hodgkin's lymphoma were infusion reactions, fever, chills, low white blood cells, infections, body aches, and tiredness. The most common side effects of Rituxan in patients with chronic lymphocytic leukemia were infusion reactions and low white blood cells. Common side effects in patients with RA include infections and infusion reactions. Patients should talk to their doctor about their medical history before starting treatment with Rituxan.
• Patients should tell their doctor about any side effect that bothers them or that does not go away. These are not all of the possible side effects with Rituxan.

Patients should read the Rituxan Full Prescribing Information including Boxed WARNINGS, and the Medication Guide at www.rituxan.com.