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IVAX Initiates Phase II Clinical Trial of Talampanel for Brain Cancer
July 10, 2003--IVAX Corporation announced today that it has initiated a phase II trial of talampanel to treat patients with brain cancer at the National Cancer Institute in Bethesda, Maryland. Dr. Howard Fine, chief of the Neuro-Oncology Branch at the National Cancer Institute, is the principal investigator of the study.
Dr. Phillip Frost, chairman and CEO of IVAX, commented, "Talampanel will represent a completely novel approach to the treatment of brain cancer."
The most common forms of brain cancer, malignant gliomas, are lethal tumors that cause progressive and ultimately fatal damage by proliferating aggressively into unaffected areas, and by causing damage to vital brain structures.
Malignant glioma cells secrete a neurotransmitter called "glutamate" and have, on their surface, receptors that bind glutamate. Pre-clinical studies have suggested that interfering with glutamate may control glioma cell proliferation and invasion, and may limit brain injury caused by glutamate excess. Talampanel blocks the effect of glutamate by blocking the AMPA subtype of glutamate receptors.
Talampanel, administered orally, has been well tolerated and has not caused bone marrow suppression and other side effects of most current forms of cancer therapy. The significant anti-seizure activity of talampanel has been previously reported, and IVAX currently has in progress an expanded phase II study of talampanel to treat refractory epilepsy and a phase II study to treat Parkinson´s Disease-associated dyskinesia.
IVAX Corporation, headquartered in Miami, Florida, discovers, develops, manufactures, and markets branded and brand equivalent (generic) pharmaceuticals and veterinary products in the U.S. and internationally.
High-grade gliomas represent an important cause of cancer morbidity and mortality in this country. Despite progress in neurosurgical and radio therapeutic techniques, there has been little improvement in the overall prognosis of patients with high-grade gliomas in the last 20 years. Standard chemotherapy is generally ineffective in this disease and thus new targets and agents with novel mechanisms of action are needed. Glutamate is the principle excitatory neurotransmitter in the brain. Membrane-bound flutamate receptors are divided into NMDA (Nmethyl-D-aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subtypes, and were previously thought to be functionally and physically limited to the synaptic surfaces of neuronal cells. Recently, however, it has been demonstrated that gliomas both secrete flutamate and have AMPA flutamate receptors that contribute to the proliferation, migration, and neurotoxicity of malignant gliomas. Inhibition of flutamate signaling has been shown to inhibit glioma growth and invasion in preclinical models. Talampanel is the prototype of a novel class of potent AMPA receptor inhibitors, and has demonstrated significant antiseizure activity and excellent tolerability in clinical studies of epilepsy. We now propose a phase II trial of talampanel as a novel new anti-glioma therapy in patients with recurrent high-grade gliomas.