SAN DIEGO, December 6, 2003 —Biogen Idec Inc. (Nasdaq: BIIB) today announced new data on Zevalin ® (Ibritumomab tiuxetan) being presented at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego, December 6-9. Among the eleven Zevalin abstracts at ASH this year are results of a new analysis supporting Zevalin’s ability to induce long-term durable remissions in patients with relapsed, refractory or transformed indolent B-cell non-Hodgkin’s lymphoma (NHL). In addition, preliminary results being reported at the meeting indicate that Zevalin has promising clinical activity in the treatment of patients with mantle cell lymphoma.
“The data presented at ASH this year continue to show that this innovative approach to cancer therapy has great clinical value,” said Arturo Molina, M.D., senior director, Medical Affairs Oncology/Hematology for Biogen Idec. “These results provide further evidence that Zevalin produces complete and enduring responses in a subset of patients with low-grade, follicular and transformed B-cell non-Hodgkin’s lymphoma, and also indicate that Zevalin may have significant utility in other types of lymphoma, including difficult-to-treat mantle cell lymphoma.”
Zevalin Induces Durable Complete Responses
Thomas E. Witzig, M.D., hematologist and professor of medicine at Mayo Clinic, Rochester, MN, delivered a poster presentation describing an analysis of long-term durable responses among a subset of patients with relapsed, refractory or transformed indolent B-cell NHL who were treated between 1996 and 1999 in four registrational trials of Zevalin. Among the group of 211 patients, Dr. Witzig and colleagues identified patients experiencing time to progression of their disease (TTP) of 12 or more months following treatment with Zevalin, and classified these as long-term responding (LTR) patients. By this defined criteria (TTP 12 months), durable responses were achieved by 78 of the 211 patients (37 percent) in the four registrational trials, with some responses lasting longer than 75 months (6.25 years).
The median follow-up for patients with long-term responses at the time of the analysis was 45.6 months (range, 12.7 to 75.5+). The median duration of response and TTP for LTR patients were 28.1 months (range, 10.5 to 74.3+) and 29.3 months (range, 12.1 to 75.5+), respectively. This compared favorably to the median duration of response (DR) to the last prior therapy for LTR patients, which was 12 months. The complete response (CR/CRu) rate for LTR patients was 66 percent, and the median DR and TTP were 29.3 months (range, 10.8 to 74.3+) and 31 months (range, 12.1 to 75.5+), respectively, for patients who achieved a CR/CRu. The median DR and TTP in ongoing responders were 48 months (range, 40 to 74.3+) and 50.4 months (range, 41 to 75.5+), respectively.
“We’re encouraged to see that more than one-third of patients treated with Zevalin achieved durable long-term responses, with some responses lasting five or more years,” said Dr. Witzig.
The four registrational trials involved more than 30 academic and community cancer centers in the United States and included the only randomized clinical trial to date comparing a radioimmunotherapy to another standard therapy (Rituximab). A high proportion of the patients in the trials were greater than 60 years old and had received three or more prior therapies.
Zevalin Shows Promising Activity in Patients with Mantle Cell Lymphoma
Anas Younes, M.D., professor of medicine at The University of Texas M. D. Anderson Cancer Center in Houston, delivered a poster presentation describing preliminary results of a phase II study evaluating the efficacy and safety of Zevalin in patients with relapsed and refractory mantle cell lymphoma.
At the time of analysis, 13 patients were enrolled in the study, 12 of whom were evaluable for treatment response and toxicity. Evaluable patients were heavily pre-treated, with a median number of three prior therapies (range of 1-6), and a median age of 64 years. Most of the 12 patients had not responded to their last treatment regimen. Of these 12 patients treated with Zevalin, three achieved complete remissions, and one had a partial remission (25 percent overall response rate). Responses lasted for 9, 6, 5+ and 4+ months. One patient had a minor response lasting for 8+ months, and two other patients had stable disease lasting for 11 and 6+ months. Responses were observed in patients receiving doses of either 0.3mCi/kg or 0.4mCi/kg.
Zevalin was well tolerated by patients in the study, with the most common toxicities being hematologic. As is the case in patients with other types of non-Hodgkin’s lymphoma receiving Zevalin, nadir platelet count and neutrophil count was delayed until six to eight weeks after therapy. Three of the 12 patients required one-to-three platelet transfusions, and one patient was admitted to the hospital with neutropenic fever.
“Mantle cell lymphoma remains a very challenging disease to manage with existing therapies,” said Dr. Younes. “We’re excited to see that even in heavily pretreated patients, Zevalin shows significant clinical activity, inducing complete responses in some patients. We look forward to exploring the uses of this agent earlier in the course of this disease with the hope of achieving even better responses.”
On February 19, 2002, the U.S. Food and Drug Administration (FDA) approved Zevalin, a new type of targeted cancer therapy called radioimmunotherapy, making it the first commercially available radioimmunotherapy for the treatment of B-cell non-Hodgkin’s lymphoma (NHL). A unique treatment regimen for patients with certain types of B cell NHL, the Zevalin Therapeutic Regimen combines a monoclonal antibody with a radioisotope. The monoclonal antibody in Zevalin recognizes and attaches to a particular cell-surface part of a B cell called the CD20 antigen. This allows Zevalin to specifically target B cells, destroying the malignant NHL B cells and also normal B cells. The generic name for Zevalin is Ibritumomab tiuxetan. Today, Zevalin is being investigated in multiple clinical trials at major medical centers in the U.S. and in a variety of treatment strategies, including combinations with front-line and salvage chemotherapy regimens and as part of autologous and allogeneic stem cell transplantation. Schering AG, Biogen IDEC’s corporate partner outside the US, is sponsoring additional studies to evaluate the efficacy and safety of Zevalin in relapsed diffused aggressive NHL and in an adjuvant setting to increase response duration after front-line chemotherapy in follicular NHL. Data from many of these studies are being reported at ASH this year.
Zevalin Safety Profile
In safety data based upon 349 patients, the most serious adverse reactions of the Zevalin therapeutic regimen were primarily hematologic, with grade 4 neutropenia, thrombocytopenia, and anemia occurring in 30%, 10% and 3% of patients treated at the 0.4 mCi/kg dose, respectively. Infusion-related toxicities were typically grade 1 or 2 and were associated with pre-administration of Rituximab (Rituxan). The risk of hematologic toxicity correlated with the degree of bone marrow involvement prior to Zevalin therapy. Seven percent of patients were hospitalized with infection (3% of these had neutropenia) and fatal cerebral hemorrhage (less than 1%) has occurred in a minority of patients in clinical studies. Myelodysplasia or acute myelogenous leukemia was observed in 1% of patients (8 to 34 months after treatment).
Zevalin should only be used by health care professionals qualified by training and experience in the safe use of radionuclides. Fatal Infusion Reactions: Rare deaths have occurred within 24 hours of Rituximab infusions. These fatalities were associated with an infusion reaction symptom complex that included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Prolonged and Severe Cytopenias: Yttrium-90 Zevalin administration results in severe and prolonged cytopenias in most patients.
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For full prescribing information, including Boxed Warnings, please call 1-877-878-4332. For more information on Zevalin, visit www.zevalin.com.