Threshold Pharmaceuticals Positive Glufosfamide Results From a Phase 2 Clinical Trial Presented at European Cancer Conference
REDWOOD CITY, Calif., Sept. 26 -- Threshold Pharmaceuticals today announced that results from a Phase 2 trial of glufosfamide plus gemcitabine were presented at the European Cancer Conference (ECCO) annual meeting in Barcelona, Spain.
In the Phase 2 clinical trial of glufosfamide in combination with gemcitabine for the treatment of advanced pancreatic cancer, six-month and one-year survival were 50% (95% CI: 31-67%) and 32% (95% CI: 16 - 49%), respectively. Median progression-free and overall survival were 3.7 and 6.0 months.
"We are encouraged by the results of this Phase 2 study, especially with respect to the one-year survival data which was higher than expected compared to previous studies of either gemcitabine alone or in combination with tarceva," said Barry Selick, Ph.D., chief executive officer of Threshold. "Based on these findings we believe that glufosfamide should have a role in the treatment of pancreatic cancer and, taken together with our Phase 3 results, we will be exploring the best options for its continued development in the treatment of this disease".
In a poster session at ECCO, Dr. Elena (Gabi) Chiorean, Indiana University Cancer Center, Indianapolis, IN, presented the Phase 2 results in a poster entitled, "Glufosfamide (GLU) plus gemcitabine (GEM) in pancreatic adenocarcinoma: results of a Phase 2 trial". In the clinical trial, 29 patients were treated, of which 28 patients with pancreatic adenocarcinoma previously untreated with chemotherapy were evaluated for response. Overall, 6 of 28 patients (21%; 95% CI: 8-41%) achieved a partial response including one unconfirmed partial response. Median duration of confirmed responses was 8.4 months. In addition, 11 of 28 patients (39%) experienced stable disease (duration 1.2+ to 12.6+ months). Objective response was assessed radiologically after every two cycles (8 weeks) of therapy. A partial response is characterized as a decrease in size by 30% of the sum of the longest diameters of target lesions, the absence of progression of all non-target lesions and no new lesions.
Grade 3 and 4 neutropenia occurred in 8 (28%) and 15 (52%) patients. Grade 3 and 4 thrombocytopenia occurred in 8 (28%) and 2 (7%) patients. Five patients (18%) had a glufosfamide-related serious adverse event (SAE), which included renal tubular acidosis (RTA) with renal failure (2 patients), RTA alone, vomiting or nausea. Three patients died from an SAE unrelated to glufosfamide. Another patient developed an SAE of renal failure after hypotension associated with pulmonary embolus. The creatinine clearance (CrCL) fell below 60 mL/min in 10 of 27 (37%) patients with CrCL greater than or equal to 60 at baseline.
These data indicate that glufosfamide plus gemcitabine may benefit patients with chemotherapy naÃƒÂ¯ve pancreatic adenocarcinoma. Hematologic and renal toxicity may be greater than would be expected with either agent alone although the small numbers preclude definitive conclusions. No unanticipated adverse events based on previous experience with glufosfamide were observed.
The Phase 2 poster is available on the Threshold website at http://investor.thresholdpharm.com/calendar.cfm.
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.
About Pancreatic Cancer
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.
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).
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, 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 time and expense required to conduct such clinical trials and analyze data, issues arising in the regulatory or manufacturing process and the results of such clinical trials (including product safety issues and efficacy results). 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.