FDA Approves Two New Indications for Rituxan in Patients With NHL
SOUTH SAN FRANCISCO, Calif. and CAMBRIDGE, Mass., September 29, 2006 -- Genentech, Inc. and Biogen Idec, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved, after a Priority Review, two additional uses for Rituxan (rituximab) for patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL). One new indication for Rituxan is for first-line treatment of previously-untreated patients with follicular NHL in combination with CVP (cyclophosphamide, vincristine and prednisolone) chemotherapy. The second new indication is for the treatment of low-grade NHL in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP chemotherapy.
"The goal of treating low-grade or follicular NHL, a chronic cancer marked by multiple recurrences, is to delay disease progression for as long as possible," said Howard Hochster, M.D., Professor of Medicine and Clinical Pharmacology, New York University School of Medicine and Cancer Institute. "These approvals enable doctors and patients to select among different treatment options with Rituxan in the front-line setting. As we demonstrated in the Eastern Cooperative Oncology Group trial, the use of extended Rituxan dosing following induction CVP chemotherapy in patients who reached stable disease or better has been shown to decrease the risk of disease progression, relapse or death."
In February 2006, Rituxan in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or other anthracycline-based chemotherapy was approved as first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL). Rituxan was approved in 1997 as a single agent for patients with relapsed or refractory, low-grade or follicular CD20- positive, B-cell NHL.
"Nearly 10 years after Rituxan’s initial approval, these new indications highlight the clinical benefit of Rituxan as part of first-line therapy for the treatment of low-grade or follicular non-Hodgkin’s lymphoma, providing patients additional options to fight this chronic disease," said Hal Barron M.D., Genentech senior vice president, development and chief medical officer. "The approvals are the result of an extraordinary collaboration between Biogen Idec, Genentech, the Eastern Cooperative Oncology Group, clinical investigators, the FDA, and most importantly, the patients who participated in the clinical trials."
"These approvals further illustrate our commitment to optimizing treatment for patients with B-cell-related diseases," said Arturo Molina, M.D., Biogen Idec’s Senior Director, Hematology/Oncology, Medical Research/Clinical Development.
The FDA approval of Rituxan as a first-line treatment in previously- untreated patients with follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy is based on data from a Phase III, randomized, controlled study of 322 patients. The study evaluated the first-line use of Rituxan in combination with CVP chemotherapy (R-CVP) versus CVP chemotherapy alone. All patients received up to eight three-week cycles of CVP chemotherapy. Patients in the R-CVP arm received Rituxan 375 mg/m2 on Day 1 of each treatment cycle.
- R-CVP improved median progression-free survival to 2.4 years from 1.4 years for CVP chemotherapy alone.
- R-CVP reduced the risk of disease progression, relapse or death by 56 percent compared to CVP chemotherapy alone (hazard ratio = 0.44 p<0.0001).
The following adverse events occurred more frequently (greater than or equal to 5%) in patients receiving R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs.6%), flushing (15% vs. 3%), rigors (10% vs. 2%), pruritis (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%).
The FDA approval of Rituxan for the treatment of low-grade, CD20-positive, B-cell NHL in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP chemotherapy, is based on a Phase III, randomized, controlled Eastern Cooperative Oncology Group study of 322 patients. Study participants received Rituxan 375 mg/m2 given in four weekly infusions, every six months for up to 16 doses, or observation. Rituxan reduced the risk of disease progression, relapse or death by more than 50 percent over observation (hazard ratio estimate in the range of 0.36 - 0.49).
The following adverse events were reported more frequently (greater than or equal to 5%) in patients receiving Rituxan following CVP compared with those who received no further therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritis (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%), Neutropenia was the only Grade 3 or 4 adverse event that occurred more frequently (greater than or equal to 2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%).
About Non-Hodgkin’s Lymphoma
An estimated 360,000 Americans have NHL and more than 58,000 new cases are diagnosed annually. Approximately 85 percent of all cases of NHL involve abnormal immune cells called B-cells. Of those diagnosed with NHL, about 30 percent of patients have a slow-growing, but incurable (low-grade) form of the disease -- the most common type is called follicular lymphoma (FL). Although FL progresses slowly, the median survival time is seven to 10 years. In addition, relapse is common and less than half of FL patients who experience a relapse will survive for five years. Approximately 31 percent of those diagnosed with NHL have DLBCL, a faster-growing subtype of NHL that multiplies and spreads rapidly in the body, and if left untreated, can be fatal.
Rituxan Safety Profile
The safety profile of Rituxan has been established in more than 960,000 patient exposures over a period of nine years.
In non-Hodgkin’s lymphoma, the majority of patients experience infusion- related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like illness, fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention.
In general, the adverse events observed in patients with RA were similar in type to those seen in patients with NHL. The most common adverse events observed in patients treated with Rituxan in RA clinical trials were infusion reactions and infections. No significant change in average immunoglobulin levels was observed in Rituxan-treated patients in clinical trials. There was no increase in hematologic malignancies, demyelinating events or risk of opportunistic infections (including tuberculosis) in Rituxan-treated patients over 24 weeks of treatment. Although five percent of Rituxan-treated patients developed human anti-chimeric antibodies (HACA), this was not associated with loss of clinical response or additional safety observations.
Severe infusion reactions have been reported in patients treated with Rituxan, some with fatal outcomes in patients with NHL. These severe reactions typically occur during the first infusion. The most severe manifestations and sequelae include pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid events. Patients who develop clinically significant infusion reactions should have their Rituxan infusion discontinued and receive medical treatment. Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of tumor lysis syndrome following treatment with Rituxan. Severe mucocutaneous skin reactions, some with fatal outcome, have been reported in association with Rituxan treatment. Patients experiencing a severe mucocutaneous reaction should not receive any further infusions and seek prompt medical evaluation. Abdominal pain, bowel obstruction and perforation, in some cases leading to death, were observed in patients receiving Rituxan in combination with chemotherapy for diffuse large B-cell, CD20-positive, NHL. Other serious or potentially life-threatening adverse reactions that have been reported following Rituxan therapy include Hepatitis B reactivation with fulminant hepatitis, other viral infections, and cardiac arrhythmias.
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 hematologic malignancies as well as autoimmune diseases with significant unmet medical needs, including systemic lupus erythematosus, lupus nephritis, 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 NHL and in February 2006, Rituxan received FDA approval for the treatment of DLBCL in combination with CHOP or other anthracycline-based chemotherapy regimens in previously untreated patients. Also in February 2006, Rituxan in combination with methotrexate (MTX) was approved to reduce signs and symptoms in adult patients with moderately-to-severely active RA who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. It was approved in the European Union under the trade name MabThera.
Posted: September 2006
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