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
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. Other serious and life-threatening side effects with Rituxan include: hepatitis B virus reactivation, heart problems, infections, 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.
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.*
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 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 therapy can result in serious side effects, some which can be life-threatening. These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B infection that may become active again, other infections, heart problems, serious kidney problems, and serious stomach and bowel problems.

The most common side effects of RITUXAN in clinical trials of patients with non-Hodgkin's lymphoma (NHL) were 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.

The most common side effects of Rituxan in clinical trials of patients with CLL were side effects from the infusion and low blood cell counts. Most side effects from the infusion happened within 24 hours of the start of the infusion, and included nausea, fever, chills, low blood pressure, vomiting, and difficulty breathing.

Most people experienced at least one serious side effect. CLL patients who were older than 70 years of age had more serious side effects compared to patients 70 or younger. The most frequently reported serious side effect was low blood cell counts.

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