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SOURCE: Pharmacyclics, Inc.
Pharmacyclics Announces Baseline Characteristics From Xcytrin Phase III Trial At ASTRO Meeting
SAN FRANCISCO, Nov. 7, Pharmacyclics, Inc.today announced baseline results from its pivotal prospective, randomized, controlled Phase III clinical trial with its lead investigational agent, Xcytrin® (motexafin gadolinium) Injection, for the potential treatment of brain metastases (i.e. cancer that has spread to the brain from another part of the body).
The company also announced updated Phase I clinical trial results suggesting the potential utility of Xcytrin in treating glioblastoma multiforme (i.e., GBM, primary brain tumor), the most common primary nervous system tumor in adults. These results were presented at the 43rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO).
Baseline data from the company´s pivotal Phase III Xcytrin trial in brain metastases were presented today at the ASTRO meeting. The characteristics of 426 evaluable patients were described and indicate that a substantial majority of patients have neurologic impairment at presentation. Survival and time to neurologic progression are the co-primary endpoints of the study, and meeting either of these endpoints is adequate for FDA approval. Pharmacyclics plans to announce top-line safety and efficacy results from this trial by the end of this year.
Patients in the trial underwent a battery of neurocognitive tests at baseline prior to randomization (i.e., Xcytrin plus whole brain radiation or whole brain radiation alone) to assess memory, verbal fluency, visual-motor scanning speed, executive function, motor speed and dexterity.
Administration of these tests was feasible in untreated patients with brain metastases, taking about 20-40 minutes to perform. Baseline data revealed substantial impairment of neurocognitive function in these patients, which was especially evident in terms of fine motor control, memory and executive function. The degree of impairment in recall, recognition and motor dexterity was similar to that observed in patients with recurrent GBM.
Results indicate a strong correlation between tumor volume and neurocognitive function. Greater tumor volume and impaired neurocognitive function were also associated with decreased, self-reported quality of life as measured with the FACT-BR standardized tool to assess activities of daily living.
"These results confirm that neurocognitive function is clinically meaningful and correlates with tumor volume, which is a known prognostic feature in patients with brain metastases," said principal investigator Minesh Mehta, M.D., associate professor and interim chair, Department of Human Oncology, University of Wisconsin Medical School. "The volume rather than the number of tumors appears to determine the degree of neurocognitive impairment, so to the degree we can effectively shrink these tumors, we should be able to significantly impact the time to neurologic progression endpoint."
Updated results of a Phase I dose-escalation trial to assess the safety and tolerability of Xcytrin for the potential treatment of GBM were presented yesterday at ASTRO. The 30 patients with newly-diagnosed GBM enrolled in this study received an injection of Xcytrin once a day for 5 - 10 days, then three times per week, for a total of 10 - 22 doses. Radiation therapy was given two to five hours after Xcytrin daily for 6.5 weeks. The treatment was well tolerated and median survival for the first 28 patients is 16.8 months, which compares favorably to a median survival rate of about 10-11 months reported in the literature for a similar patient population. Among the limited number of side effects observed were non-dose related rash and finger blisters.
The trial also demonstrated Xcytrin´s unique tumor selectivity with the drug being taken up and retained in glioblastoma, but not in the normal brain, as has been observed in brain metastases and other tumors.
"We are particularly encouraged that after over one year of follow up, median survival is holding up well in this very sick patient population," said lead investigator Judith Ford, M.D., Ph.D., assistant professor, Department of Radiation Oncology, UCLA Medical Center in Los Angeles, who presented the data. "These results suggest a potential role for this agent in treating patients who suffer from primary brain tumors, one of the most difficult-to-treat tumors. We look forward to confirming these findings in a larger controlled trial."
Based on these findings, Pharmacyclics continues to investigate Xcytrin for the treatment of GBM and recently completed enrollment in a 25-patient Phase II study. The company expects to complete analysis of the safety data from this trial by the first quarter of next year. If these data confirm those observed in the Phase I trial, the company plans to initiate a pivotal Phase III trial for this investigational use.
About Xcytrin
Xcytrin, the first of a new class of drugs called texaphyrins, selectively accumulates in cancer cells and disrupts cellular metabolism by a unique mechanism of action. By interfering with the flow of energy in cancer cells, Xcytrin makes the tumor potentially more responsive to the effects of radiation and chemotherapy without increasing damage to normal tissue.
About Brain Metastases and Primary Brain Tumors
Brain metastases is one of the most common conditions treated with radiation therapy. There are about 170,000 cases per year and the incidence is increasing. The most common causes of brain metastases are lung and breast cancer. 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 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. There are about 17,000 new cases of primary brain and nervous system tumors each year in the U.S. and more than 13,000 deaths occur from these types of malignancies.
About Pharmacyclics
Pharmacyclics is a pharmaceutical company developing products to improve upon current therapeutic approaches to cancer, atherosclerosis and retinal disease. The company´s products are rationally designed, ring-shaped small molecules called texaphyrins that disrupt the bioenergetic processes of diseased cells, such as cancer and atherosclerotic plaque. When activated by various forms of energy, including X-ray and light, these texaphyrins can help to reduce or eliminate the diseased tissue. More information about the company, its technology, and products can be found on its web site at www.pcyc.com.
NOTE: The statements made in this press release about progress and reports of clinical trial results and product development activities, other than statements of historical fact, are forward-looking statements. The forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements, including risks associated with the initiation, timing, and results of clinical trials, the progress of research and development programs, the regulatory approval process in the U.S. and other countries, and future capital requirements. For further information about risks that may affect the actual results achieved by Pharmacyclics, please see the company´s reports as filed with the U.S. Securities and Exchange Commission from time to time, including but not limited to, its reports on Form 10-Q and 10-K. Pharmacyclics®, Xcytrin®, and the "pentadentate" logo are registered trademarks of Pharmacyclics, Inc.
SOURCE: Pharmacyclics, Inc.