Pharmacyclics Announces Publication of Xcytrin Phase Ib/II Study Results In Journal of Clinical Oncology

Xcytrin Appears to Increase Tumor Response Rate and Reduce Death Due to Tumor

Progression in Patients With Brain Metastases



Apr 02, 2001, 01:00 ET from Pharmacyclics, Inc.

    SUNNYVALE, Calif., April 2 /PRNewswire/ --
 Pharmacyclics, Inc. (Nasdaq:   PCYC), announced today that the results of a
 multi-center Phase Ib/II clinical trial of its investigational agent
 Xcytrin(R) (motexafin gadolinium) Injection were published in this week's
 issue of the Journal of Clinical Oncology.  The published results indicate
 that Xcytrin, when administered in combination with standard whole brain
 radiation therapy, increased local tumor control, as evidenced by a high tumor
 response rate (i.e., significant tumor shrinkage) and low rate of death due to
 tumor progression in the brain in patients with brain metastases
 (i.e. cancer that spreads to the brain from another part of the body).
     "We are particularly pleased to see the high tumor response rate, which is
 nearly double what we have observed in the literature with radiation alone,"
 said Minesh Mehta, M.D., associate professor and interim chair,
 Department of Human Oncology, University of Wisconsin Comprehensive Cancer
 Center, Madison, one of the study's lead investigators.  "Based on these
 encouraging results, we conducted a large multi-center international Phase III
 study designed to measure survival and time to neurologic progression in a
 similar patient population.  Enrollment in this 428-patient trial has been
 completed, and we expect to report results by the end of this year."
     Xcytrin is the first of a new class of drugs called texaphyrins that
 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 more responsive to the effects of radiation and
 chemotherapy without increasing damage to normal tissue.
 
     Key Study Findings
     Sixty-one patients with brain metastases were enrolled in the combined
 Phase Ib/II trial.  For 10 days, daily intravenous injections of Xcytrin were
 administered, followed by whole brain radiation treatment each day.
 Thirty-nine patients were enrolled in the Phase Ib portion of the trial
 intended to determine optimal dosing and tumor localization using magnetic
 resonance imaging (MRI), and 22 patients were enrolled in the Phase II portion
 of the trial designed to assess tumor response and side effect profile.
     Eighteen Phase II patients were evaluable for tumor response based on
 follow-up MRI scans.  After a two-month follow up, tumor response, defined as
 greater than 50 percent reduction in tumor volume, was seen in
 13 of 18 patients (72 percent), significantly higher than the 43 percent
 reported in previous studies of patients treated with standard whole brain
 radiation therapy alone.  Death due to tumor progression in the brain was just
 12 percent, compared to a rate of about 50 percent reported in previous
 studies of patients treated with radiation alone.  MRI scanning showed visual
 enhancement of the brain metastases for 56 days following administration of
 Xcytrin, demonstrating how the drug localizes selectively and is retained in
 the tumors.
     The treatment was well tolerated.  The most common side effects observed
 were discoloration of the skin, urine and eyes due to the dark green color of
 the drug.  The discoloration developed gradually after repeated drug dosing,
 and cleared three to four days after the last dose.
     "This is the first treatment of its kind that appears to enhance the
 beneficial effects of radiation therapy in a clinical setting," said
 Dr. Patrice Carde, Chef de Service, Department of Medicine, Institut Gustave
 Roussy, Villejuif, France, lead author of the study.
 
     Brain Metastases:  An Increasing Clinical Problem
     Approximately 170,000 patients are diagnosed with brain metastases each
 year in the United States.  This number is increasing as cancer patients live
 longer due to new treatment advances made in the last several years.  However,
 there are few treatment options for patients whose cancer has advanced and
 spread to the brain.
     Metastases in the brain are one of the most devastating consequences of
 cancer, affecting up to 40 percent of all cancer patients.  The majority of
 brain metastases originate in breast and lung cancers.  Brain metastases occur
 when cancer cells from the primary site migrate (often through the blood
 stream) and travel to the brain, where they remain and grow.  Patients with
 brain metastases may suffer devastating complications from uncontrolled
 progression of tumor growth in the brain; these complications include
 headaches, seizures, paralysis, blindness, neurocognitive deterioration and
 death.  The goal of whole brain radiation therapy is to reverse or prevent
 neurological deterioration and prevent death due to tumor progression in the
 brain.
 
     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 the progress and
 reports of the results of clinical trials and preclinical studies 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, and the regulatory approval process in the
 United States and other countries.  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(R), Xcytrin(R), and the "pentadentate" logo(R) are
 registered trademarks of Pharmacyclics, Inc.
 
 

SOURCE Pharmacyclics, Inc.
    SUNNYVALE, Calif., April 2 /PRNewswire/ --
 Pharmacyclics, Inc. (Nasdaq:   PCYC), announced today that the results of a
 multi-center Phase Ib/II clinical trial of its investigational agent
 Xcytrin(R) (motexafin gadolinium) Injection were published in this week's
 issue of the Journal of Clinical Oncology.  The published results indicate
 that Xcytrin, when administered in combination with standard whole brain
 radiation therapy, increased local tumor control, as evidenced by a high tumor
 response rate (i.e., significant tumor shrinkage) and low rate of death due to
 tumor progression in the brain in patients with brain metastases
 (i.e. cancer that spreads to the brain from another part of the body).
     "We are particularly pleased to see the high tumor response rate, which is
 nearly double what we have observed in the literature with radiation alone,"
 said Minesh Mehta, M.D., associate professor and interim chair,
 Department of Human Oncology, University of Wisconsin Comprehensive Cancer
 Center, Madison, one of the study's lead investigators.  "Based on these
 encouraging results, we conducted a large multi-center international Phase III
 study designed to measure survival and time to neurologic progression in a
 similar patient population.  Enrollment in this 428-patient trial has been
 completed, and we expect to report results by the end of this year."
     Xcytrin is the first of a new class of drugs called texaphyrins that
 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 more responsive to the effects of radiation and
 chemotherapy without increasing damage to normal tissue.
 
     Key Study Findings
     Sixty-one patients with brain metastases were enrolled in the combined
 Phase Ib/II trial.  For 10 days, daily intravenous injections of Xcytrin were
 administered, followed by whole brain radiation treatment each day.
 Thirty-nine patients were enrolled in the Phase Ib portion of the trial
 intended to determine optimal dosing and tumor localization using magnetic
 resonance imaging (MRI), and 22 patients were enrolled in the Phase II portion
 of the trial designed to assess tumor response and side effect profile.
     Eighteen Phase II patients were evaluable for tumor response based on
 follow-up MRI scans.  After a two-month follow up, tumor response, defined as
 greater than 50 percent reduction in tumor volume, was seen in
 13 of 18 patients (72 percent), significantly higher than the 43 percent
 reported in previous studies of patients treated with standard whole brain
 radiation therapy alone.  Death due to tumor progression in the brain was just
 12 percent, compared to a rate of about 50 percent reported in previous
 studies of patients treated with radiation alone.  MRI scanning showed visual
 enhancement of the brain metastases for 56 days following administration of
 Xcytrin, demonstrating how the drug localizes selectively and is retained in
 the tumors.
     The treatment was well tolerated.  The most common side effects observed
 were discoloration of the skin, urine and eyes due to the dark green color of
 the drug.  The discoloration developed gradually after repeated drug dosing,
 and cleared three to four days after the last dose.
     "This is the first treatment of its kind that appears to enhance the
 beneficial effects of radiation therapy in a clinical setting," said
 Dr. Patrice Carde, Chef de Service, Department of Medicine, Institut Gustave
 Roussy, Villejuif, France, lead author of the study.
 
     Brain Metastases:  An Increasing Clinical Problem
     Approximately 170,000 patients are diagnosed with brain metastases each
 year in the United States.  This number is increasing as cancer patients live
 longer due to new treatment advances made in the last several years.  However,
 there are few treatment options for patients whose cancer has advanced and
 spread to the brain.
     Metastases in the brain are one of the most devastating consequences of
 cancer, affecting up to 40 percent of all cancer patients.  The majority of
 brain metastases originate in breast and lung cancers.  Brain metastases occur
 when cancer cells from the primary site migrate (often through the blood
 stream) and travel to the brain, where they remain and grow.  Patients with
 brain metastases may suffer devastating complications from uncontrolled
 progression of tumor growth in the brain; these complications include
 headaches, seizures, paralysis, blindness, neurocognitive deterioration and
 death.  The goal of whole brain radiation therapy is to reverse or prevent
 neurological deterioration and prevent death due to tumor progression in the
 brain.
 
     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 the progress and
 reports of the results of clinical trials and preclinical studies 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, and the regulatory approval process in the
 United States and other countries.  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(R), Xcytrin(R), and the "pentadentate" logo(R) are
 registered trademarks of Pharmacyclics, Inc.
 
 SOURCE  Pharmacyclics, Inc.

RELATED LINKS

http://www.pcyc.com