"We are excited to initiate this trial for elesclomol in prostate cancer," said Eric Jacobson, M.D., Senior Vice President and Chief Medical Officer, Synta. "The positive results from our prior, Phase 2b trial in metastatic melanoma, a notoriously difficult-to-treat cancer, combined with a strong, emerging scientific picture of how elesclomol selectively targets and kills cancer cells, suggest that ROS-induced apoptosis is a promising, new approach to treating high-ROS cancers. These include melanoma, prostate, breast, ovarian, and other cancers that we are actively considering for investigation as we advance this program in the clinic."
"Prostate cancer is a particularly promising opportunity for elesclomol because there is a high unmet need in the hormone refractory population, because it is a cancer known to be high in ROS, and because taxanes are a widely accepted treatment option in this disease. The underlying biology suggests a strong rationale for combining elesclomol and taxanes, and we have seen evidence of strong synergistic activity in our preclinical models," said Dr. Jacobson.
The open-label Phase 1/2 study of elesclomol in combination with docetaxel in approximately 34 patients with advanced metastatic, hormone refractory prostate cancer is designed to identify the maximum tolerated dose of elesclomol in combination with docetaxel based on a once-a-week, one-hour intravenous dosing schedule. In the second phase of the study, additional subjects will be added at the maximum tolerated dose level to further evaluate the safety and tolerability of the combination as well as to evaluate anti-tumor activity based on progression as defined by the Prostate Cancer Clinical Trials Working Group (PCWG2), prostate-specific antigen (PSA) levels and overall survival. The study uses a new water soluble (sodium salt) formulation that allows for more convenient administration in combination with other anti-cancer agents.
"Cancer cells are known to operate at a much higher level of oxidative stress than normal cells," said John Fruehauf, M.D., Ph.D., Associate Professor of Clinical Medicine at the University of California Cancer Center in Irvine. "Exploiting this fundamental difference utilizing a known oxidative stress inducer such as elesclomol provides a new approach to treating a range of cancers, particularly those which are known to operate at a high level of oxidative stress."
Prostate cancer is the most common type of cancer found in American men, after skin cancer. The American Cancer Society estimates there will be approximately 186,320 new cases of prostate cancer in the United States in 2008. About 28,660 men will die of this disease this year. One man in six will get prostate cancer during his lifetime, and one man in 35 will die of this disease.
"Despite advancements in early detection and treatment, prostate cancer is now the leading cause of cancer deaths of men in the United States, and there is clearly still an unmet medical need for better treatment options, particularly for later stage patients for whom treatment options are limited," said the principal investigator on the trial, Paul G. Corn, M.D., Ph.D., Assistant Professor, MD Anderson Cancer Center at the University of Texas, in Houston. "We are excited to be studying elesclomol in this setting and are hopeful its novel mechanism may prove to be effective in treating this difficult cancer."
Elesclomol is a novel, injectable, investigational drug candidate that triggers apoptosis (programmed cell death) in cancer cells. Cancer cells operate at high levels of reactive oxygen species, or oxidative stress. Elesclomol is believed to act by increasing the level of oxidative stress in cancer cells even further, beyond sustainable levels, inducing apoptosis. This mechanism of action, called oxidative stress induction, represents a novel way of selectively targeting and killing cancer cells.
In a double-blind, randomized, controlled Phase 2b clinical trial in 81 patients with stage IV metastatic melanoma, elesclomol in combination with paclitaxel met the primary endpoint, doubling the median time patients survived without their disease progressing, compared to paclitaxel alone (p = 0.035). The most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea, and anemia.
A pivotal Phase 3 clinical trial of elesclomol in combination with paclitaxel in patients with stage IV metastatic melanoma (the SYMMETRYSM trial) is ongoing; Phase 2 trials in other indications, and in combination with other agents, are planned. Elesclomol has received Fast Track and Orphan Drug designation from the FDA for metastatic melanoma, and the Phase 3 SYMMETRY trial has completed a Special Protocol Assessment process with the FDA. Information about the SYMMETRY trial can be found at www.symmetrymelanomastudy.com, or www.clinicaltrials.gov (NCI identifier # NCT00522834).
Ongoing Clinical Trials
Elesclomol is currently in a global, pivotal Phase 3 trial called SYMMETRYSM. The SYMMETRY study is being conducted at approximately 150 centers worldwide to determine the efficacy of elesclomol in combination with paclitaxel for the treatment of patients with metastatic (Stage IV) melanoma. Elesclomol has received Fast Track and Orphan Drug designation from the FDA for metastatic melanoma, and the Phase 3 SYMMETRY trial has completed the Special Protocol Assessment review process with the FDA. Additional investigations to evaluate elesclomol as a therapy for other cancers are currently being planned. Information about the SYMMETRY trial can be found at www.symmetrymelanomastudy.com, or www.clinicaltrials.gov.
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a diverse pipeline of clinical- and preclinical-stage drug candidates with distinct mechanisms of action and novel chemical structures. All Synta drug candidates were invented by Synta scientists using our compound library and discovery capabilities. For more information, please visit www.syntapharma.com.
Safe Harbor Statement
This media release may contain forward-looking statements about Synta Pharmaceuticals Corp. Such forward-looking statements can be identified by the use of forward-looking terminology such as "will", "would", "should", "expects", "anticipates", "intends", "plans", "believes", "may", "estimates", "predicts", "projects", or similar expressions intended to identify forward-looking statements. Such statements, including statements relating to the timing and progress of our clinical and preclinical programs, reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such forward-looking statements, including those described in "Risk Factors" of our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission. Synta undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise, except as required by law.
SOURCE: Synta Pharmaceuticals Corp.
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125
MacDougall Biomedical Communications
Doug MacDougall, 781-235-3060