Cell Therapeutics, Inc. (CTI) announced an agreement with Bayer Schering Pharma to gain access to Bayer's phase III Zevalin ([90Y]-ibritumomab tiuxetan) First-line Indolent Trial, FIT data. CTI expects that the data from the trial will be appropriate for CTI to begin discussions with the US Food and Drug Administration (FDA) regarding the potential for a supplemental Biologics License Application (sBLA) for Zevalin based on Bayer's trial results.

Based on these data the European Medicines Commission recently approved Zevalin for use as consolidation therapy after remission induction in previously untreated patients with follicular lymphoma. The benefit of Zevalin following rituximab in combination with chemotherapy has not been established.

CTI acquired the US sales and marketing rights to Zevalin in December of 2007 from Biogen Idec. Zevalin is currently approved in the United States for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL), including patients with rituximab refractory follicular NHL. Zevalin is also indicated, under accelerated approval, for the treatment of relapsed or refractory, rituximab-naive, low-grade and follicular NHL based on studies using an endpoint of overall response rate, which is a surrogate for progression free survival. Studies to determine whether the Zevalin therapeutic regimen confers an effect on progression-free survival are ongoing.

The FIT study, which evaluated the use of Zevalin as first-line consolidation therapy in follicular lymphoma patients, was sponsored by Bayer Schering Pharma AG, who has exclusive rights to Zevalin in all countries of the world except the US. CTI has now entered into an agreement with Bayer Schering Pharma to get access to this data. Under the terms of the agreement, CTI will make an initial payment to Bayer Schering Pharma with an additional payment upon FDA approval of a sBLA for Zevalin based on the FIT trial results. CTI also will pay Bayer royalties on net product sales up to a specified aggregate amount.

"We believe that gaining access to these important Zevalin trial data and regulatory documents will allow for the potential to expand the label in the US to include consolidation of first-line therapy, as Bayer Schering Pharma did in Europe, and may give more patients access to the potential benefits of Zevalin," said James A. Bianco, MD, president and CEO of Cell Therapeutics. "We are pleased with Bayer's willingness to support our efforts to potentially broaden US patient access to this important therapeutic, and delighted to be working with such a talented group of dedicated healthcare professionals."

Cell Therapeutics has requested a meeting with the Food and Drug Administration (FDA) to discuss expanding the label for Zevalin in the US to include consolidation following first-line treatment of follicular lymphoma based on the FIT trial data. If approved, this new indication has the potential to increase the market for Zevalin in the US.

The multinational, randomized phase III First-line Indolent Trial (FIT) evaluated the benefit and safety of a single infusion of Zevalin in patients with CD20-positive follicular lymphoma who had achieved a partial remission or a complete remission after receiving standard first-line chemotherapy regimens. The FIT trial results were presented in one oral and two poster presentations at the American Society of Hematology (ASH) conference in December 2007. The FIT trial demonstrated that when used as a first-line consolidation therapy for patients with follicular lymphoma, Zevalin significantly improved the median progression-free survival time from 13.5 months (control arm) to 37 months.

The primary investigators of the study concluded that Zevalin consolidation of first remission in advanced stage follicular lymphoma is highly effective, resulting in a total complete response (CR + CRu) rate of 87 percent and prolongation of median progression-free survival (PFS) by approximately two years, with a toxicity profile comparable to that seen with Zevalin's use in approved indications. Zevalin-treated patients had reversible Grade 3 or 4 haematologic side effects including neutropenia in 67 per cent, thrombocytopenia in 61 percent, and anaemia in 3 per cent. Nonhematologic toxicities were 23.5 per cent Grade 3, and Grade 3/4 infection was 7.9 per cent.

Zevalin (Ibritumomab Tiuxetan) is a form of cancer therapy called radioimmunotherapy and is indicated as part of the Zevalin therapeutic regimen for treatment of relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma, including patients with rituximab refractory follicular NHL. Zevalin is also indicated, under accelerated approval, for the treatment of relapsed or refractory, rituximab-naive, low-grade and follicular NHL based on studies using a surrogate endpoint of overall response rate nonhematologic toxicities were 23.5 per cent Grade 3, and Grade 3/4 infection was 7.9 per cent. It was approved by the FDA in February of 2002 as the first radioimmunotherapeutic agent for the treatment of NHL.

Rare deaths associated with an infusion reaction symptom complex have occurred within 24 hours of rituximab (Rituxan) infusions. Yttrium-90 Zevalin administration results in severe and prolonged cytopenias in most patients. Severe cutaneous and mucocutaneous reactions have been reported. The most serious adverse reactions of the Zevalin therapeutic regimen were primarily haemtologic, including neutropenia, thrombocytopenia and anaemia. Infusion-related toxicities were associated with pre-administration of rituximab. The risk of haematologic toxicity correlated with the degree of bone marrow involvement prior to Zevalin therapy. Myelodysplasia or acute myelogenous leukaemia was observed in two per cent 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.