Landmark Study Demonstrates Potential of Radioimmunotherapy for Treatment of Indolent B-Cell Non-Hodgkin’s Lymphoma
Zevalin® First-Line Indolent (FIT) Phase III Clinical Trial results published in Journal of Clinical Oncology
Seattle, October 16, 2008 —Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) announced today that the Journal of Clinical Oncology has published the results of the First-line Indolent Trial (FIT) demonstrating that use of Zevalin®([90Y]-ibritumomab tiuxetan) in consolidation therapy after remission induction in previously untreated patients with follicular non-Hodgkin’s lymphoma provided important patient benefits including a significant improvement in progression free survival. A companion editorial discussed the growing evidence for the efficacy of radioimmunotherapy (RIT) in B-cell lymphomas. Cell Therapeutics has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for use of Zevalin in first-line consolidation therapy based on the FIT data.
Oliver W. Press, M.D., Ph.D., Member of the Fred Hutchinson Cancer Research Center and Professor at the University of Washington, commented in his editorial that the studies “confirm and extend prior data demonstrating the tremendous potential of RIT in the treatment of B-cell NHL at diagnosis and after relapse at both conventional and myeloablative doses. Despite the overwhelming body of evidence, however, RIT remains underused in the United States and other countries. The reasons for this underuse have been widely debated but seem to be related, at least partially, to logistic issues involved in the transfer of care from the hematologist/oncologist to the nuclear medicine physician, concerns about inadequate reimbursement by Medicare for RIT, and exaggerated emphasis on delayed effects such as marrow damage and secondary malignancies. It is hoped that studies such as those in this issue would encourage wider appreciation and use of RIT.”
“We couldn’t agree more with Dr. Press’ comments about the importance of these results for patients with newly diagnosed follicular NHL as well as his views as to why this important therapeutic option is underutilized by physicians,” noted James Bianco, M.D., CEO of Cell Therapeutics. “We have been working with CMS in making reimbursement for RIT similar as any biologic agent, and with the FDA on reviewing the FIT results for a potential indication as consolidation therapy following first-line therapy in newly diagnosed patients as well as removing the need for the pre-treatment nuclear medicine scan on the basis of studies such as FIT and accumulated safety data. We believe these steps will allow office based hematologist/oncologists the ability to offer RIT with Zevalin to their patients eliminating many of the current concerns that have limited patient access to this important treatment option.”
The multinational, randomized phase III First-line Indolent Trial (FIT) evaluated the benefit and safety of a single infusion of Zevalin in 414 patients with CD20-positive follicular non-Hodgkin’s lymphoma who had achieved a partial response or a complete response after receiving a variety of first-line chemotherapy regimens. The FIT trial demonstrated that when used as a first-line consolidation therapy for patients with follicular non-Hodgkin’s lymphoma, Zevalin significantly improved the median progression-free survival time from 13.3 months (control arm) to 36.5 months (Zevalin arm) (p<0.0001). This advantage was observed regardless of whether patients were in partial remission (29.3 v 6.2 months p<0.0001without Zevalin) or complete remission (53.9 v 29.5 months p=0.0154). Furthermore, Zevalin consolidation converted 77 percent of patients who had achieved only a partial remission (PR) after induction therapy to complete remission / complete remission unconfirmed (CR/CRu). Nearly all subgroups appeared to benefit regardless of prognostic score.
The primary investigators of the study concluded that Zevalin consolidation of first remission in advanced stage follicular non-Hodgkin’s 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 hematologic side effects including neutropenia in 67 percent, thrombocytopenia in 61 percent, and anemia in 3 percent of patients. Non-hematologic toxicities were 24% Grade 3 and 5% Grade 4. The Grade 3/4 infection rate was 8%.
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. The Zevalin therapeutic regimen has been given 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.
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-naïve, low-grade and follicular NHL based on studies using a surrogate endpoint of overall response rate. 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 hematologic, including neutropenia, thrombocytopenia and anemia. Infusion-related toxicities were associated with pre-administration of rituximab. The risk of hematologic toxicity correlated with the degree of bone marrow involvement prior to Zevalin therapy. Myelodysplasia or acute myelogenous leukemia was observed in 2 percent 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.
Patients and healthcare professionals can visit www.zevalin.com for more information.
About Non-Hodgkin’s Lymphoma
Non-Hodgkin’s lymphoma (NHL) is caused by the abnormal proliferation of white blood cells and normally spreads through the lymphatic system, a system of vessels that drains fluid from the body. NHL can be broadly classified into two main forms – aggressive NHL, a rapidly spreading acute form of the disease, and indolent NHL, which progresses more slowly. According to the National Cancer Institute’s SEER database there were nearly 400,000 people in the U.S. with NHL in 2004. The American Cancer Society estimates that 66,120 people will be diagnosed with NHL in 2008 and more than 19,000 are expected to die.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.celltherapeutics.com.
This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of Zevalin include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with Zevalin in particular including, without limitation, the potential for Zevalin FIT data to be acceptable to the FDA for this expanded indication or any other indication, the potential that the FDA will not grant priority review to the sBLA determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, and costs of developing, producing and selling Zevalin. There is also a risk that even if label expansion of Zevalin is approved, it may not result in a significant market increase for the drug due to the presence of other treatment options, failure to gain market acceptance and other factors. You should also review the risk factors listed or described from time to time in the Company’s filings with the Securities and Exchange Commission including, without limitation, the Company’s most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
Lindsey Jesch Logan
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Posted: October 2008