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Priority Review Designation Granted to Rituximab in Rheumatoid Arthritis
The FDA grants Priority Review status to products that are considered to be potentially significant therapeutic advancements over existing approved therapies in the treatment, diagnosis or prevention of a disease. Based on the designation of Priority Review, the FDA has up to six months from the submission date, or by late February 2006, to take action on the Rituxan sBLA submission. The companies submitted the sBLA on August 29, 2005.
The sBLA submission was based primarily on 24-week results of a multi-center, randomized, double-blind, placebo-controlled Phase III study known as REFLEX. In the trial, patients who received a single course of two infusions of Rituxan with a stable dose of methotrexate (MTX) displayed a statistically significant improvement in symptoms, as measured by American College of Rheumatology (ACR) 20 response, compared to those who received placebo and MTX. The results of the REFLEX trial will be presented at the ACR annual meeting in San Diego in November 2005.
The most common side effects in the Rituxan arm of REFLEX included headache, upper respiratory tract infection and nasopharyngitis. The rate of serious adverse events reported was comparable across treatment arms. Analysis of the REFLEX 24-week data did not reveal any unexpected safety signals, and the companies continue to monitor the long-term safety of Rituxan in all clinical trials.
RA is a debilitating autoimmune disease that affects more than two million Americans(1) and hinders the daily activities of sufferers. RA occurs when the immune system inappropriately attacks joint tissue, causing painful chronic inflammation and irreversible destruction of cartilage, tendons and bones, often resulting in disability. While RA has traditionally been considered a T-cell-mediated disease, emerging research suggests that other immune cells called B-cells may play multiple roles in the pathophysiology of RA, including autoantibody production, T-cell activation and cytokine production. 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, eyes and bone marrow.
Rituxan is a therapeutic antibody that targets and selectively depletes CD20-positive B-cells without targeting stem cells or existing plasma cells. Rituxan is also being studied in other autoimmune diseases, including lupus, 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, non-Hodgkin's lymphoma (NHL). It was approved in the European Union under the trade name MabThera® in June 1998. 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 has been used to treat more than 730,000 patients 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.
Rituxan Safety Profile in non-Hodgkin's Lymphoma
In NHL, the majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion.
These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan infusion discontinued and receive medical treatment.
In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B-cell lymphomas, particularly NHL and chronic lymphocytic leukemia. Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment, including a skin biopsy to guide therapy.
Source: Biogen Idec, Inc. and Genentech, Inc.