Zevalin

SAN DIEGO, Calif. -- Biogen Idec, Inc. (Nasdaq: BIIB) today announced new data on ZEVALIN(R) (ibritumomab tiuxetan) being presented at the 46th Annual Meeting of the American Society of Hematology (ASH) in San Diego, December 4-7. Among the abstracts at ASH this year are:

--Positive results from a large open-label, multicenter Phase II study of ZEVALIN in older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

--New data on frontline use of ZEVALIN in patients diagnosed with follicular lymphoma

--Updated results from an ongoing trial of ZEVALIN in relapsed mantle cell lymphoma

--Up-to-date long-term responder data from the four registrational trials of ZEVALIN

"We're continuing to gain valuable knowledge about the utility of ZEVALIN in a variety of lymphoma subtypes and in front-line and relapse treatment strategies including transplantation," said Arturo Molina, M.D., senior director, Medical Affairs Oncology/Hematology for Biogen Idec. "The new data at ASH this year reinforces our belief that this innovative approach to cancer therapy has great value in clinical practice."

ZEVALIN Appears Effective in Most Common Lymphoma Subtype - Diffuse Large B-cell Lymphoma

Franck Morschhauser, M.D., Hematology and Nuclear Medicine, Hospital Claude Huriez, CHU in Lille, France, delivered an oral presentation describing results of a prospective, single-arm, open-label, non-randomized, multicenter Phase II trial that evaluated the efficacy and safety of the ZEVALIN therapeutic regimen in elderly patients with histologically confirmed first relapsed or primary refractory DLBCL for whom stem cell transplantation was not appropriate.

DLBCL is the most common lymphoma subtype and accounts for 50% of all non-Hodgkin's lymphomas among older patients. The prognosis is poor for patients who have relapsed or who are refractory following CHOP, the standard first-line combination chemotherapy for this disease. The prognosis is especially poor for those who are not candidates for stem cell transplantation. At present, there is no standard second-line treatment regimen for older patients in this situation.

"The results of this study demonstrate that the ZEVALIN therapeutic regimen is effective as a single agent for patients with diffuse large B-cell lymphoma, the most frequent form of NHL, and one for which the prognosis is quite poor following initial relapse," said Dr. Morschhauser.

The trial comprised a total of 104 patients who were divided into two groups: those previously treated with chemotherapy alone (n=76), and those previously treated with chemotherapy and rituximab (RITUXAN(R)) (n=28). The median age of patients in the trial was 72. All patients were to receive a single dose of yttrium-90 ZEVALIN. Of the 104 patients, all were evaluable for safety and 103 were evaluable for efficacy. An overall response rate to ZEVALIN of 44% was observed for the entire study population, patients previously treated with chemotherapy (i.e., CHOP or CHOP-like regimen) with or without rituximab. The best response to ZEVALIN (ORR = 58%) was observed in patients whose lymphoma progressed more than a year after initially presenting with the disease.

There were four deaths due to serious AEs; three in patients with grade 4 thrombocytopenias; another died of bleeding, however, this AE was determined not to be related to the study drug. Non-hematologic adverse events (AEs) were generally mild or moderate. The incidence of severe infection was low with 7% of patients hospitalized for severe infection during the study.

Front-line Therapy with ZEVALIN Appears to Produce High Response Rates in Follicular Lymphoma

John W. Sweetenham, M.D., Hematology/Oncology, Arizona Cancer Center, Tucson, AZ, delivered a poster presentation detailing the results of a study of ZEVALIN in combination with rituximab maintenance therapy in patients with previously untreated low grade follicular non-Hodgkin's lymphoma. Patients were eligible for the trial if they presented with histologically confirmed, previously untreated, stage III or IV, low-grade follicular lymphoma and a need for therapeutic intervention because of constitutional symptoms, evidence of disease progression or organ dysfunction directly attributable to NHL. Patients were excluded if there was evidence of transformation to aggressive disease.

To date, 10 patients with low-grade follicular lymphoma have been treated with ZEVALIN and 8 are evaluable to treatment response. The median age of patients was 58 years (age range, 40-82) and 50% of patients had stage IV disease. Of the eight patients, five (62%) achieved a complete response (CR) and three (38%) had a partial response (PR). Toxicities were primarily hematologic with grade 3 cytopenia occurring in 38% (3/8) of patients.

Updated Data Reinforces Previous Data on ZEVALIN in Mantle Cell Lymphoma

Yasuhiro Oki, M.D., in the Department of Lymphoma and Myeloma at The University of Texas M.D. Anderson Cancer Center in Houston, delivered a poster presentation describing updated results of an ongoing Phase II study evaluating the efficacy and safety of ZEVALIN in patients with relapsed and refractory mantle cell lymphoma.

To date, 15 patients have enrolled in the trial and all are evaluable for both treatment response and safety. Patients in the study were heavily pre-treated, having failed a median of three prior regimens, and older, with a median age of 66 years (age range, 51-77).

Major objective responses were seen in five patients (33%), including three CRs and two CRus. Two additional patients had a minor response, and 1 patient had stable disease. The median duration of response for patients achieving a complete response (confirmed (CR) and unconfirmed (CRu)) was 5.7 months. Three patients are still free of disease progression at 123,200 and 380 days.

ZEVALIN was generally well tolerated by patients in the study, with the most common toxicities being hematologic. Three of the 15 patients required one to three platelet transfusions, and one patient was admitted to the hospital with neutropenic fever.

ZEVALIN Has Potential to Produce Long-Term Responses in Relapsed or Refractory B-cell NHL

Russell J. Schilder, M.D., in the Department of Medical Oncology at the Fox Chase Cancer Center, Philadelphia, PA, delivered a poster presentation describing ongoing analysis of long-term responses to ZEVALIN among a subset of 211 patients with relapsed, refractory or transformed indolent B-cell NHL treated between 1996 and 1999 in four registrational trials of the therapy. With ongoing follow-up, long-term durable responses have been observed, but, until now, they have not been more fully characterized.

Long-term responding (LTR) patients were defined as those experiencing a time-to-progression of their disease (TTP) of 12 or more months following treatment with ZEVALIN. By this defined criteria (TTP > or = 12 months), durable responses were achieved by 78 (37%) of the 211 patients in the study. Characteristics of these LTR patients were as follows: median age 58 years (range, 24 to 80), 44% were more than 60 years old, 55% were male and 41% had lymphoma involvement in their bone marrow. LTR patients had a median of two prior regimens (range, 1-9): 59% had > or = 2 prior therapies, 33% had > or = 3 prior therapies and 37% had no response to their last prior therapy. Thirty percent (30%) of LTR patients had bulky disease (tumor size > 5 cm) and 83% had stage III/IV disease.

The complete response rate among LTR patients was 65%, and the median DR and TTP were 29 and 31 months respectively, for CR/CRu patients.

At the time of analysis, the median duration of response (DR) and TTP for LTR patients was 28 months (range, 11-80) and 29 months (range, 12-82), respectively, with a median follow up of 50 months (range, 13-82). Fifty-nine (59) of the 78 LTR patients (76%) had follicular lymphoma.

Compared to the overall LTR patient population, LTR patients with follicular lymphoma had similar disease characteristics, DR, TTP and CR/CRu rates.

About ZEVALIN

On February 19, 2002, the ZEVALIN therapeutic regimen became the first radioimmunotherapy approved by the U.S. Food and Drug Administration (FDA). Radioimmunotherapy is an innovative form of cancer treatment that offers an option to patients with certain types of B-cell non-Hodgkin's lymphoma who have failed to adequately respond to other cancer therapies. ZEVALIN is FDA-approved for the treatment of patients with relapsed or refractory low grade, follicular or transformed B cell non-Hodgkin's lymphoma, including patients with rituximab (RITUXAN) refractory follicular non-Hodgkin's lymphoma. Determination of the effectiveness of ZEVALIN in a relapsed or refractory patient population is based on overall response rates. The effects of ZEVALIN on survival are not known.

The ZEVALIN therapeutic regimen combines a monoclonal antibody with a radioisotope. The monoclonal antibody in ZEVALIN recognizes and attaches to a particular cell-surface protein on B cells called the CD20 antigen. This allows ZEVALIN to specifically target B cells, destroying malignant NHL B-cells and also normal B cells. The generic name for ZEVALIN is ibritumomab tiuxetan.

Today, ZEVALIN is being investigated in a variety of lymphoma subtypes including diffuse large B cell lymphoma. ZEVALIN is also being studied in a number of different treatment strategies including combinations with front-line and salvage chemotherapy regimens and as part of autologous and allogeneic stem cell transplantation in both indolent and aggressive lymphoma subtypes.

ZEVALIN Safety Profile

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.

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. With long-term follow-up of the registrational trials, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has been observed in 3% of patients. The annualized incidence of MDS/AML is consistent with that expected from this population of heavily treated NHL patients.

About Biogen Idec

Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing, and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare.

For ZEVALIN product labeling, press releases and additional information about the company, please visit http://www.biogenidec.com.

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