Glufosfamide Results From Phase 3 Clinical Trial Presented At European Cancer Conference (ECCO)

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials;  Conferences
Article Date: 28 Sep 2007 - 0:00 PDT

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Threshold Pharmaceuticals, Inc. (Nasdaq: THLD), announced that detailed results from a Phase 3 trial of glufosfamide were presented at the European Cancer Conference (ECCO) annual meeting in Barcelona, Spain.

As announced on February 26, 2007, the Phase 3 trial of glufosfamide showed that the overall survival in patients with metastatic pancreatic cancer who had relapsed after gemcitabine chemotherapy was 18% higher in the glufosfamide arm compared to those who received best supportive care (BSC), but the result did not reach statistical significance. Detailed analysis of the data from that study suggests that glufosfamide is active in certain subgroups of patients.

Dr. Tudor Ciuleanu, Ion Chiricuta Cancer Institute, Medical Oncology, Cluj, Romania, gave a presentation at ECCO entitled, "Glufosfamide (GLU) in metastatic pancreatic adenocarcinoma previously treated with gemcitabine: Results of a Phase III trial" which reviewed the detailed results of the Phase 3 trial. In this multi-national, randomized, open-label Phase 3 trial, 303 patients with metastatic pancreatic cancer who had relapsed after standard gemcitabine-containing systemic chemotherapy were randomized to receive glufosfamide every three weeks plus BSC (n=148) or BSC alone (n=155).

The primary efficacy comparison of overall survival was based on 261 deaths and did not reach statistical significance (p=0.19); the hazard ratio of glufosfamide to BSC was 0.85 (95% confidence interval of 0.66 to 1.08). The median survival of patients who were treated with glufosfamide was 105 days (3.45 months) versus 84 days (2.76 months) for the patients who received BSC.

Dr. Ciuleanu presented data that outlined longer overall survival in certain subgroups of patients receiving glufosfamide. In general, patients with better prognosis showed a greater treatment effect than those with poorer prognosis. Surprisingly, however, a subgroup of diabetic patients taking glucose-lowering agents (primarily sulfonylureas) indicated much improved survival with glufosfamide. The median overall survival of these patients who were treated with glufosfamide (n=7) was 13.7 months (95% CI: 2.8 to NA) versus 2.4 months (95% CI: 1.5 to 3.4) for these patients who received BSC alone (n=14).

Glufosfamide combines the active part of ifosfamide, a member of a widely used class of chemotherapy drugs known as "alkylators", with a glucose molecule. Because of its glucose component and a tumor cell's increased need for glucose, glufosfamide may be preferentially transported into tumors compared to most normal tissues. Inside cells, the linkage between glucose and the alkylator is cleaved to release the active drug.

The subgroup analysis suggests that glucose lowering agents may preferentially enhance the efficacy of glufosfamide in this patient population. The Company believes that glufosfamide should have a role in the treatment of pancreatic cancer and will explore the best options for its continued development in the treatment of the disease.

"We recognize the pitfalls of subgroup analyses in clinical studies that do not reach their primary endpoint", said Michael Brawer M.D., chief medical officer of Threshold. "However, today's presentation combined with the supportive data from an earlier Phase 2 study with glufosfamide in the first- line pancreatic setting in which prolonged survival was noted in two of three subjects on glucose lowering agents, indicate that this subgroup of patients may warrant further investigation."

About Pancreatic Cancer and Diabetes

The American Cancer Society estimates that 37,170 patients will be diagnosed with pancreatic cancer in the United States in 2007, and approximately 33,370 patients will die from the disease. Only 15-20% of newly diagnosed patients are eligible for surgery, which is typically followed by radiation and chemotherapy. Patients with inoperable pancreatic cancer are treated with radiation and chemotherapy, or in the case of metastatic disease, chemotherapy alone as the advantages of radiation are reduced. More than 50% of people with pancreatic cancer have hyperglycemia or a diagnosis of diabetes.

About Threshold Pharmaceuticals

Threshold is a biotechnology company focused on the discovery and development of small molecule therapeutics for the potential treatment of cancer. By selectively targeting abnormally-proliferating tumor cells, the Company's drug candidates are designed to be potentially more effective and less toxic to healthy tissues than conventional treatments. For additional information, please visit our website (http://www.thresholdpharm.com).

Forward-Looking Statements

Except for statements of historical fact, the statements in this press release are forward-looking statements, including statements regarding Threshold's product candidates, clinical trial progress and results, clinical trial plans, potential therapeutic uses and benefits of our product candidates and financial projections. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward- looking statements. Potential risks and uncertainties include, but are not limited to, Threshold's ability to commence, enroll or complete its anticipated clinical trials, the results of those clinical trials (including product safety issues and efficacy results), the time and expense required to conduct such clinical trials and analyze data and issues arising in the regulatory or manufacturing process. The scientific information discussed in this news release related to our product candidate is preliminary and investigative. The product candidate is not approved by the U.S. Food and Drug Administration (FDA), and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidate. Only the FDA can determine whether the product candidate is safe and effective for the use(s) being investigated. Further information regarding these and other risks is included under the heading "Risk Factors" in Threshold's Quarterly Report on Form 10-Q, which was filed with the Securities Exchange Commission on August 7, 2007 and is available from the SEC's website (http://www.sec.gov) and on our website (http://www.thresholdpharm.com) under the heading "Investors." We do not intend to update any forward-looking statement made in this news release.

Threshold Pharmaceuticals, Inc
http://www.thresholdpharm.com