Phase I/II Study of Continuous Oral Dosing of an Irreversible CYP17 Inhibitor, Abiraterone, in Castration-Resistant Prostate Cancer Patients Incorporating the Evaluation of Androgens and Steroid Metabolites in Plasma and Tumor and the Study of Circulating Tumor Cells
The Phase I/II trial of CB7630 was conducted at The Institute of Cancer Research and at The Royal Marsden NHS Foundation Trust in the United Kingdom. In the trial, CB7630 was administered orally, once daily, to chemotherapy-naive patients with castration resistant prostate cancer (CRPC), who had progressive disease despite treatment with LHRH analogues and multiple other hormonal therapies, including antiandrogens, diethylstilboestrol and dexamethasone. To date, a total of 42 patients have been treated in the Phase I/II trial, including 15 patients treated in the Phase I stage of the trial and 27 patients treated in the Phase II stage of the trial. In his poster presentation, Dr. Gerhardt Attard from The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust in the United Kingdom reported that in the 42 patients treated in this trial, CB7630 was well tolerated at doses as high as 2000 mg/day with minimal toxicity. Moreover, no dose limiting toxicity has been observed in the trial to date.
In the 34 patients who were evaluable for response in the Phase I/II trial, 22 patients (65%) experienced a confirmed decline in prostate specific antigen (PSA) levels of greater than 50%, with 10 of the 34 patients (29%) experiencing PSA declines of greater than 90%. Of the 20 evaluable patients with measurable tumor lesions, treatment with CB7630 resulted in partial radiological responses (as measured by the RECIST criteria) in 11 patients (55%), with 7 patients demonstrating ongoing stable disease and 3 patients experienced regressing bone disease. Several patients treated with CB7630 also experienced improvement in pain and a notable reduction in opioid use. Circulating tumor cells (CTC) were detected in 16 of 34 patients and changes in CTC counts were shown to correlate with changes in PSA.
Currently 30 of the 42 evaluable patients (71%) in the Phase I/II trial remain on study and continue to be treated with CB7630. Of the 15 patients in the Phase I stage of the trial, 9 patients (60%) are still receiving treatment with CB7630 with the average patient having received the drug for over 9.7 months, including 5 patients having received the drug for over 12 months. Of the 12 patients who started the trial longer than 9 months ago, 8 patients (67%) have shown a confirmed response that has lasted longer than 9 months and these responses continue in all but one of these patients.
In his poster, Dr Attard also provided an update on the Phase II trial of CB7630 in patients with advanced prostate cancer who have failed androgen deprivation and docetaxel-based chemotherapy. The Phase II trial is being conducted at numerous locations in the United States and United Kingdom. In the trial, CB7630 is administered orally, once daily, to patients with castration refractory prostate cancer who have failed treatment with first line docetaxel based chemotherapy.
To date, 38 patients have been treated in this Phase II trial with 13 of the patients having been treated for over 3 months. Of the 38 patients who have been treated, CB7630 was well tolerated with only minimal toxicity in this post-docetaxel population. In the 13 patients who have been in the study for over 3 months, 10 patients (77%) experienced a decline in PSA levels of greater than 50%. Thirty-one of the 38 patients (82%) in this trial are still receiving treatment with CB7630. Individual patients treated with CB7630 also experienced improvement in pain and a reduction in opioid use.
Phase I Evaluation of Abiraterone Acetate (CB7630), a 17 Alpha Hydroxylase C17,20-Lyase Inhibitor as Secondary Hormonal Therapy in Castration Resistant Prostate Cancer (CPRC)
The Phase I trial was conducted at the University of California, San Francisco Comprehensive Cancer Center with Charles J. Ryan, MD, Assistant Clinical Professor of Medicine, as the principal investigator. CB7630 was administered once daily to chemotherapy-naive patients with castration refractory prostate cancer (CRPC), who had progressive disease despite treatment with LHRH analogues and multiple other hormonal therapies.
Of the 25 patients who had been enrolled in the study, 3 patients had "PSA only" disease and 22 patients had either bone or soft tissue metastases. Nineteen of the 25 patients (76%) have received 3 or more cycles of CB7630 and are evaluable for response. Sixteen of 25 patients (64%) had received prior treatment with ketoconazole. Treatment with CB7630 was found to be well tolerated at doses up to 1000 mg/day. In the 25 patients who have been treated with CB7630, 24 of 25 patients (96%) experienced a PSA decline, including 12 of 25 patients (48%) who experienced a greater than 50% decline in PSA and 3 of 25 patients (12%) who experienced a greater than 90% decline in PSA. Prior treatment with ketoconazole was not seen to impact response to abiraterone as 7 of 16 patients (44%) with prior ketoconazole exposure and 3 of 5 patients (60%) with no ketoconazole exposure experienced a greater than 50% decline in PSA. Currently 9 of the 25 patients (36%) in the Phase I trial remain on study and are continuing to be treated with CB7630.
Dr. Arie S. Belldegrun, MD, FACS, Vice Chairman of the Board of Directors of Cougar Biotechnology, said, "The interim data on CB7630 presented at the ASCO Annual Meeting continues to support the role of the drug as both a second line hormonal therapy, as well as a second line chemotherapy. We are also pleased to be able to demonstrate that CB7630 is active in patients who have failed ketoconazole, a drug that is currently widely used off-label as a secondary hormonal therapy. As both addressable patient populations (second line hormone therapy candidates and second line chemotherapy candidates) continue to represent significant unmet medical needs in CRPC, we believe that CB7630 has strong potential in both of these patient populations." Alan H. Auerbach, Chief Executive Officer and President of Cougar Biotechnology, added, "We continue to be pleased with the interim clinical data being generated on CB7630. We greatly look forward to the continued development of CB7630 in both the second line hormone therapy and second line chemotherapy settings."
About Cougar Biotechnology
Cougar Biotechnology, Inc. is a Los Angeles-based biotechnology company established to in-license and develop clinical stage drugs, with a specific focus on the field of oncology. Cougar's oncology portfolio includes CB7630, a targeted inhibitor of the 17-alpha hydroxylase/c17,20 lyase enzyme, which is currently being tested in Phase II clinical trials in prostate cancer; CB3304, an inhibitor of microtubule dynamics, which is currently in a Phase I trial in hematological malignancies and CB1089, an analog of vitamin D, which has been clinically tested in a number of solid tumor types.
Further information about Cougar Biotechnology can be found at www.cougarbiotechnology.com.
This press release contains forward-looking statements within the meaning of the Pri vate Securities Litigation Reform Act of 1995. These statements are often, but not always, made through the use of words or phrases such as "anticipates," "expects," "plans," "believes," "intends," and similar words or phrases. These forward-looking statements include, without limitation, statements related to benefits to be derived from Cougar's drug development programs, including the potential advantages of CB7630 and its potential for use in the treatment of CRPC and in second line hormone and chemotherapy treatment settings. Such statements involve risks and uncertainties that could cause Cougar's actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in clinical trials, and drug development and commercialization, including the uncertainty of whether results in testing of CB7630 will be predictive of results in later stages of development. For a discussion of these and other factors, please refer to Cougar's annual report on Form 10-KSB for the year ended December 31, 2006 as well as other subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and Cougar undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.
Cougar Biotechnology, Inc.
Alan H. Auerbach, Chief Executive Officer and President
Mariann Ohanesian, Director of Investor Relations
Russo Partners, LLC
David Schull, +1-212-845-4271
Andreas Marathovouniotis, +1-212-845-4253