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Phase III Study of Motexafin Demonstrates Positive Neurocognitive Function Results

SUNNYVALE, Calif., Jan. 5 /PRNewswire-FirstCall/ -- Pharmacyclics, Inc. (NASDAQ:PCYC) announced today the publication of positive neurocognitive function and progression results from the company's first randomized Phase 3 clinical trial of its investigational drug Xcytrin(R) (motexafin gadolinium) Injection in combination with whole brain radiation therapy (WBRT) for the treatment of brain metastases in lung cancer patients in the latest issue of the Journal of Clinical Oncology (JCO).

"This is one of the first reports of prospective neurocognitive testing and analyses in patients with brain metastases, and demonstrated that the addition of motexafin gadolinium (i.e., Xcytrin) to whole brain radiation therapy improved time to neurocognitive progression in patients with brain metastases from lung cancer," said Christina A. Meyers, Ph.D., Professor of Neuro-oncology, MD Anderson Cancer Center, Houston, Texas and lead author of the publication. "Neurocognitive function is a relatively sensitive measure of the functioning of the brain and is predictive of patient outcome."

The study describes detailed findings from neurocognitive testing performed as part of Pharmacyclics' previously published Phase 3, randomized, controlled clinical trial of 401 patients with metastatic cancer to the brain.

Based on these Phase 3 findings, Pharmacyclics, together with leading experts in radiation and medical oncology, designed and initiated a pivotal Phase 3 trial known as the SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) trial. This randomized controlled study is now enrolling patients at leading medical centers in the United States, Canada, Europe and Australia. It is designed to compare the effects of WBRT alone to WBRT plus Xcytrin for the treatment of patients with brain metastases from lung cancer with a primary endpoint of time to neurologic progression as determined by a blinded events-review committee. Neurocognitive function tests are a component of the neurologic progression endpoint. Survival and neurocognitive function will also be assessed as secondary endpoints of the trial.

In the previous Phase 3 trial, Xcytrin was found to significantly prolong the time to neurologic progression determined by both investigators and blinded events review committee in patients with brain metastases from non-small cell lung cancer. Consistent with those previously published data, time to neurocognitive progression also was improved in patients with lung cancer receiving Xcytrin and WBRT compared to those receiving WBRT alone.

In the study reported in JCO, neurocognitive function was measured at baseline prior to therapy and at regular intervals during and after therapy. Neurocognitive function tests evaluated patients' short and long term memory, verbal fluency, decision making and fine motor skills. Over 90% of patients with brain metastases exhibited impairment of one or more neurocognitive tests at baseline.

"This peer reviewed publication establishes that patients with brain metastases have serious neurocognitive impairment, and that Xcytrin may positively impact many of these performance measures, which also are being measured in the SMART trial," said Richard A. Miller, M.D., president and chief executive officer of Pharmacyclics. "Neurologic function, including neurocognitive performance, is a critically important clinical benefit assessment in patients with brain metastases. This publication follows closely upon the recent designation of Fast Track status by the U.S. Food and Drug Administration and the completion of a Special Protocol Assessment (SPA) specifying approvability of the SMART trial's primary endpoint."

About Xcytrin
Xcytrin is the first of an investigational class of drugs called texaphyrins, which are rationally designed small molecules that have a unique way of working inside diseased cells. Possessing a novel mechanism of action, Xcytrin is a tumor-targeted generator of intracellular molecules known as reactive oxygen species (ROS).

After administration, Xcytrin selectively localizes and accumulates inside cancer cells, due to their high rates of metabolism, including anaerobic glycolysis. Because Xcytrin is a paramagnetic compound, its presence is visible with magnetic resonance imaging (MRI). Studies with MRI have confirmed the selective localization of Xcytrin in primary and metastatic tumors.

Within cancer cells, Xcytrin disrupts cellular metabolism, interferes with the flow of energy, and results in the generation of ROS. This mechanism of action of Xcytrin is believed to make cancer cells more vulnerable to the oxidative stress (i.e., specific types of damage involving oxidation-reduction reactions) caused by radiation therapy and chemotherapy. The generation of ROS within cancer cells promotes a process called programmed cell death, or apoptosis, leading to the selective destruction of the cancer cells.

Preclinical studies have shown that Xcytrin enhances the efficacy of radiation therapy and that of several commonly used chemotherapy agents. Currently, Xcytrin is being investigated as a potential therapeutic in combination with radiation therapy and/or chemotherapy, monoclonal antibody therapy and as a single agent for various types of cancers in several clinical trials sponsored by Pharmacyclics and/or the National Cancer Institute.

About Brain Metastases
Brain metastases is one of the most common conditions treated with radiation therapy. There are about 150,000 to 170,000 cases per year and the incidence is increasing. The most common cause of brain metastases is lung cancer, affecting up to 90,000 patients. Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in most cases, death. Patients with brain metastases usually suffer serious deterioration of neurologic and neurocognitive function such as loss of short-term memory, compromised verbal skills and fine motor coordination, and reduction in cognitive performance. Most patients with brain metastases have multiple lesions and are not candidates for surgical resection or radiosurgery. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain.

Source: Pharmacyclics, Inc.

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