FDA accepts Zevalin supplemental biologics license application

Dec 1 2008

Cell Therapeutics, Inc. (CTI) has announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and review, and has granted priority review status for, the supplemental Biologics License Application (sBLA) for use of Zevalin ([90Y]-ibritumomab tiuxetan) as consolidation therapy for patients with follicular B-cell non-Hodgkin's lymphoma who achieve a response to first-line therapy. Priority review is granted by the FDA for a treatment that addresses a significant unmet medical need.

A Prescription Drug User Fee Act (PDUFA) target date of April 2, 2009 has been established by the FDA for a decision regarding the approval of the Zevalin sBLA. If approved, Zevalin would be the first radioimmunotherapy available to patients as first-line consolidation therapy. It is estimated that there would be approximately 18,000 additional patients that currently receive first-line treatment which would potentially be eligible to use Zevalin under the proposed expanded label.

CTI and Spectrum Pharmaceuticals, Inc. entered into an agreement to form a 50/50 owned joint venture, RIT Oncology LLC, on November 26, 2008 to commercialize and develop ZEVALIN in the United States and expects the transaction will close in early December, 2008. CTI initially acquired the US rights to Zevalin from Biogen Idec in December 2007. CTI gained access to the First-line Indolent Trial (FIT) data through an agreement with Bayer Schering Pharma AG, Germany who used the data to obtain approval for Zevalin as first-line consolidation treatment in Europe.

"We are pleased that the FDA, by granting the application priority review status, acknowledges that the use of Zevalin in the first-line consolidation setting could represent an important treatment option for follicular B-cell non-Hodgkin's lymphoma patients," said James A. Bianco, M.D., CEO of Cell Therapeutics. "In addition to shortening the timeframe for FDA review from 10 months to 6 months, it would also enable physicians to get this drug to those who may benefit from it sooner. If approved, it also pushes up our anticipated timeline for commercial launch for first-line indication by 4 months which should result in a substantial increase to our revenue forecast in 2009."

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.

About First-Line Consolidation Therapy

Consolidation therapy is a treatment given after initial induction therapy and is aimed at improving the quality of the patient response by further diminishing the number of cancer cells with the goal of extending the response duration.

About the Phase III First-line Indolent Trial (FIT)

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 standard first-line chemotherapy regimens. The FIT trial results were presented for the first time in one oral and three 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 non-Hodgkin's lymphoma, Zevalin significantly improved the median progression-free survival time from 13 months (control arm) to 37 months (Zevalin arm) (p<0.0001).

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. Nonhematologic toxicities were 24 percent Grade 3, 5 percent Grade 4, and Grade 3/4 infection was 8 percent.

About Zevalin

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 http://www.zevalin.com/ for more information.

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 in the United States 66,120 people are expected to be diagnosed with NHL in 2008. Additionally, approximately 19,160 are expected to die from this disease in 2008.