Multiple Dose Clinical Trial of TorreyPines Therapeutics'Tezampanel Demonstrates Compound is Safe and Well-Tolerated- Findings Support Continued Development for Chronic Pain and Non-Pain Indications -
LA JOLLA, Calif., February 5, 2008 /PRNewswire/ -- TorreyPines Therapeutics, Inc. today announced that data from its multiple dose clinical trial of tezampanel, an antagonist of the AMPA and kainate subgroup of glutamate receptors, show that the product candidate is safe and well-tolerated in normal male and female subjects.
These Phase I results support the company's continued development of tezampanel as a novel therapeutic for chronic pain and expand its potential therapeutic applications across a variety of persistent conditions in which activation of glutamate receptors initiates or sustains pathophysiological processes. These conditions include cancer pain and neuropathic pain, as well as non-pain conditions such as epilepsy, muscle spasticity and rigidity, and Parkinson's disease. A recently completed Phase IIb clinical trial of tezampanel in 306 patients with migraine met its primary endpoint for pain relief at two hours using a single 40 mg subcutaneous dose. In five previously conducted placebo-controlled, Phase II trials, an intravenous formulation of tezampanel demonstrated analgesic effect across all five studies using a variety of chronic pain models.
The Phase I double-blind, placebo-controlled trial enrolled 30 healthy male and female subjects in sequential, dose-escalating cohorts. Subjects received once-daily subcutaneous injections of placebo or 40 mg, 70 mg or 100 mg of tezampanel for four consecutive days, approximating exposure under steady-state pharmacokinetic conditions. Overall, tezampanel was well-tolerated. There were no dose-limiting adverse events or discontinuations from the study and reported adverse events were generally mild and transient.
"This study is an important step forward in the clinical development of tezampanel. Our ability to safely deliver multiple doses of tezampanel means that we can now pursue virtually any indication that requires chronic dosing," said Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines Therapeutics. "There is an emerging appreciation of the pathological effects of increased AMPA and kainate receptor activation by glutamate. By blocking both receptors, tezampanel and its oral prodrug, NGX426, may represent a unique and effective approach to treat a variety of chronic pain as well as non-pain conditions."
Tezampanel is the first AMPA/kainate antagonist to be studied in clinical trials for chronic pain. Both tezampanel and NGX426 represent a novel, non-opiod, non-vascular and non-serotonergic approach to treating multiple chronic pain conditions. Tezampanel and NGX426 are antagonists of a subgroup of glutamate receptors referred to as AMPA and kainate. These receptors are found in areas of the central and peripheral nervous system that are important for the transmission of pain. For example, during a migraine attack, levels of glutamate increase and activate these receptors, facilitating the transmission of pain impulses. Tezampanel, by blocking the binding of glutamate to these receptors, is believed to inhibit the transmission of pain signals that lead to migraine headaches. The blockade of similar receptors in other regions of the brain or spinal cord has been shown in animal models to attenuate pathophysiological processes such as the muscle spasticity and rigidity that occurs following stroke and spinal cord injury, or that may be associated with multiple sclerosis.
About TorreyPines Therapeutics
TorreyPines Therapeutics, Inc. is a clinical-stage biopharmaceutical company committed to the discovery, development and commercialization of small molecules. The company is developing versatile product candidates, each potentially capable of treating a number of different diseases and disorders, including chronic pain, muscle spasticity and rigidity, cognitive disorders and xerostomia, or dry mouth.
This press release contains forward-looking statements or predictions. Such forward-looking statements include statements regarding the potential for tezampanel as a treatment for migraine, the potential for NGX426 as a treatment for migraine, the potential for tezampanel to offer a unique approach to the management of pain, the potential for tezampanel or NGX426 to offer a unique approach to the management of pain and the potential timing, development and initiation of future clinical trials of tezampanel and NGX426. Such statements are subject to numerous risks, and uncertainties that may cause actual events or results to differ materially from the company's current expectations. Statements regarding TorreyPines Therapeutics' product candidates are subject to risks and uncertainties regarding development, regulatory approval and commercialization, including whether the results of the Phase IIb trial are predictive of results in subsequent trials of tezampanel, whether the results of the Phase I trial are predictive of results in subsequent trials of tezampanel or NGX426, whether further testing of tezampanel and NGX426 will result in data sufficient to support regulatory approval, whether AMPA/kainate antagonists will prove to be safe and effective treatments for migraine and other pain conditions as well as non-pain conditions, whether any preclinical studies or clinical trials, either ongoing or conducted in the future, will prove successful, and if successful, whether the results can be replicated; whether safety and efficacy profiles of any of its drug candidates will be established, or if established, will remain the same, be better or worse in future clinical trials, if any; whether pre-clinical results will be substantiated by ongoing or future clinical trials, if any, or whether any of its product candidates will be able to improve the signs or symptoms of their respective clinical indication; whether any of its product candidates will support an NDA filing, will be approved by the FDA or its equivalent, or if approved, will prove competitive in the market; or whether the necessary financing to support its drug development programs will be available. Actual results may differ materially from the above forward-looking statements due to a number of other important factors. These and other risks which may impact management's expectations are described in greater detail in the TorreyPines Therapeutics annual report on Form 10-K for the year ended Dec. 31, 2006, as well as TorreyPines Therapeutics' subsequent filings with the Securities and Exchange Commission. TorreyPines Therapeutics undertakes no obligation to publicly release the result of any revisions to such forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
Posted: February 2008