Abbott Laboratories' Atrasentan (ABT-627) Demonstrates Potential Survival Benefit in Hormone-Refractory Prostate Cancer Patients
New Phase II Results Presented for Oral Endothelin-A Receptor AntagonistABBOTT PARK, Ill., May 18, 2002 /PRNewswire-FirstCall via COMTEX/--New Phase II data presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting show that treatment with atrasentan (ABT-627), Abbott Laboratories' investigational, selective endothelin-A receptor antagonist, may provide a survival benefit in men with advanced (hormone-refractory) prostate cancer that has metastasized or spread beyond the prostate gland.
The data, presented by Michael Carducci, M.D., associate professor at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and a co-lead investigator in the study, show that men who fully adhered to the protocol and received atrasentan experienced a median survival benefit of approximately three months compared to those who received placebo. All patients also received standard of care, which is a continuation of hormone therapy plus supportive care, when appropriate. Atrasentan is currently under further investigation in two, large, multinational Phase III clinical trials.
"Although this study was not designed to assess survival, we are optimistic about the potential survival advantage demonstrated with atrasentan in this trial," said Joel Nelson, M.D. professor and chairman of urology, University of Pittsburgh Cancer Institute, and the other co-lead investigator in the study. "These data further substantiate the potential clinical benefit of atrasentan for men with advanced prostate cancer. We look forward to further understanding the potential for atrasentan based on ongoing Phase III trials."
The data presented are from a Phase II study of 288 patients randomized to receive an oral, once-daily dose of 2.5 mg or 10 mg of atrasentan, or placebo together with standard of care. All patients participating in the study had prostate cancer that had metastasized (spread beyond the prostate gland) and was hormone-refractory (no longer responded to hormone therapy). After completion of the Phase II study, patients were eligible to receive atrasentan therapy in an open-label extension study.
In 244 evaluable patients, average survival was 583 days for those who received atrasentan compared to 500 days for those who received standard of care (p<0.05). The evaluable group, which was defined prior to study unblinding, included patients who met prespecified inclusion criteria and did not have any major violations of the study protocol. A similar survival trend was noted in the intent-to-treat group (which included all 288 patients originally enrolled in the study, regardless of meeting inclusion criteria or protocol violations).
"These findings add to the growing body of evidence that endothelin is a key target for therapeutic intervention in prostate cancer patients and that atrasentan may provide an option for men who currently have limited treatment options," said Perry Nisen, M.D., Ph.D., divisional vice president, Global Oncology Development at Abbott Laboratories. "This is a truly new approach to prostate cancer treatment since the advent of hormone therapy 60 years ago. It exemplifies researchers' ability to take a basic science discovery and translate it into research that has a potential clinical benefit."
Earlier analysis of the Phase II atrasentan study presented at the 2001 ASCO Annual Meeting showed that an evaluable subset of patients who received an oral dose of 2.5 mg or 10 mg of atrasentan once daily experienced a longer median time to clinical progression of the disease, 184 and 196 days respectively, compared to 129 days for patients receiving placebo with standard of care (p<0.05).
Adverse events were mild to moderate in severity. The most common adverse events associated with the 10 mg dose of atrasentan compared to placebo were peripheral edema (swelling, 35 percent vs. 14 percent), rhinitis (runny nose, 28 percent vs. 13 percent) and headache (20 percent vs. 10 percent) and were associated with only one treatment discontinuation.
"Atrasentan is the most advanced compound in Abbott's oncology research program," said Dr. Nisen. "We are working to discover and develop innovative, less toxic cancer therapies than we have today to enable patients to live with cancer, not die from it."
Atrasentan belongs to a class of drugs called endothelin receptor antagonists. Endothelin receptor antagonists block the activity of endothelin, a protein produced in the body that stimulates the growth and spread of cancer cells. Cancer cells produce endothelin, and concentrations of this protein and its receptor are increased in prostate cancer patients. There are two endothelin receptors, ET-A and ET-B. The ET-A receptor appears to be important in prostate cancer progression and atrasentan is highly selective for ET-A.
Atrasentan is the first endothelin antagonist to be investigated for the treatment of cancer. It is currently being studied in two pivotal Phase III clinical trials in patients with advanced prostate cancer and has been granted "fast track" designation for review by the U.S. Food and Drug Administration (FDA). Phase II studies in earlier stages of prostate cancer and in combination with other agents are also underway. For more information about the atrasentan trials, please call 1-86-ONCOLOGY or visit www.abbott.com.
In addition to prostate cancer, preclinical studies suggest that atrasentan may be able to play a role in other cancers, including ovarian, renal, lung, colorectal, breast and brain. Phase II trials in these cancers, as well as studies of atrasentan in combination with other agents for advanced prostate cancer, are planned for 2002.
Abbott Laboratories is committed to the discovery and development of innovative treatments to help patients in the fight against cancer. Abbott's oncology research is focused on developing targeted, less toxic therapies than are currently available. These approaches address multiple phases of cancer progression, including angiogenesis (new blood vessel formation), cell cycle control and programmed cell death (apoptosis). Atrasentan is one of several compounds in Abbott's rapidly growing oncology pipeline in all stages of development.
Abbott's Oncology Franchise extends beyond pharmaceutical research to supportive care products and diagnostics. Abbott currently manufactures products for pain management, including patient-controlled analgesia pumps, and markets tests for detection of cancer, including a prostate-specific antigen (PSA) test. Abbott's innovative genomic tests include UroVysion, for monitoring the recurrence of bladder cancer, and PathVysion, for detecting the HER-2 gene, which may predict potential treatment benefit in women with breast cancer. Abbott also markets nutritional products designed to meet the unique dietary needs of cancer patients.
Abbott Laboratories is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals, nutritionals, and medical products, including devices and diagnostics. The company employs approximately 70,000 people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the company's Web site at www.abbott.com .
SOURCE Abbott Laboratories
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