Today, Cougar Biotechnology, Inc. (NASDAQ:CGRB) unveiled the results from its ongoing Phase II clinical trial drug CB7630 (abiraterone acetate). The data was presented at the Prostate Cancer Foundation Scientific Retreat in Lake Tahoe, Nevada.
The clinical trial, which is centered at the M.D. Anderson Cancer Center in Texas and was designed to look at the associations between serum and microenvironment (bone marrow) androgen concentrations and the clinical response to CB7630. CB7630 was administered orally in combination with prednisone to men with castration resistant prostate cancer (CRPC), who had progressive disease despite treatment with LHRH analogues (traditional hormone blockade drugs) and multiple other therapies.
The trial enrolled 44 men with very advanced disease. All the subjects had radiological evidence of metastatic disease with bone metastases. Thirty-eight patients (86%) had at least 10 metastatic bone lesions, 7 patients (16%) had metastases in the liver and 14 patients (32%) had lymph node metastases. Twenty-five (57%) of the 44 patients had received prior treatment with ketoconazole and/or diethylstilbesterol (DES) and 38 patients (86%) had received prior treatment with chemotherapy, with 27 patients (61%) having received two or more prior chemotherapy regimens before entering the trial.
The preliminary results were presented in a poster presentation entitled, “Identification of an androgen withdrawal responsive phenotype among patients with castrate resistant prostate cancer (CRPC) treated with abiraterone acetate, a selective CYP17 inhibitor (COU-AA-BMA).” The poster presenter Dr. Eleni Efstathiou, a researcher from the University of Texas MD Anderson Cancer Center presented data on the 41 evaluable men treated to date in the trial. Of the 41 evaluable patients, 21 patients (51%) experienced a confirmed decline in prostate specific antigen (PSA) levels of greater than 50% with a median duration of 6+ months. In addition, 5 patients (12%) experienced PSA declines of greater than 90%. Of the 41 evaluable patients, 24 (59%) experienced an improvement in performance status.
Of the 16 evaluable patients with bone metastases, after 6 months of treatment 4 patients (25%) showed an improvement in their bone scan and 11 patients (69%) showed a stable bone scan. Also, 5 of 5 patients with lymph node metastases showed stable disease after 6 months of treatment with CB7630 and 1 of 2 patients with liver metastases demonstrated a partial radiological response (as measured by the RECIST criteria).
Both serum and bone marrow testosterone levels were measured before and after treatment with CB7630. A decline in both serum and bone marrow testosterone levels to below detectable levels (<10ng/ml) was seen in all patients in the trial. Also, patients with depleted baseline bone marrow testosterone levels (<10ng/ml) appeared to progress earlier when treated with CB7630 (p=0.05) compared to patients with measurable baseline bone marrow testosterone levels. Further examination of the bone marrow biopsies of patients treated with CB7630 in this study revealed both overexpression of androgen receptor and CYP17 overexpression. Alan H. Auerbach, Chief Executive Officer and President of Cougar Biotechnology, said, "The data from our COU-AA-BMA trial of CB7630 presented at the Prostate Cancer Foundation Scientific Retreat continues to support the potential role of the drug in the treatment of CRPC. We continue to be pleased with the strong evidence of antitumor activity in patients with chemotherapy refractory disease, which represents a significant unmet medical need in prostate cancer." Arturo Molina, M.D., M.S., FACP, Cougar's Chief Medical Officer and Executive Vice President of Clinical Research and Development, added, " The identification of CYP17 expression in CRPC tumor metastases and observation that both serum and bone marrow testosterone levels decline after CB7630 therapy suggests that treatment with CB7630 results in the inhibition of adrenal and intra-tumoral androgen synthesis." On June 4, 2008, I wrote a post titled: “Abiraterone Acetate- Clinical Trial Of A Cellular Hormone Blockade For Prostate Cancer”. In that post, I expressed my hope that CB7630 would prove to be a powerful new drug in our arsenal, as we are very limited in the number and effectiveness of approved drugs to treat advancer prostate cancer. I felt that this type of drug is particularly important because it holds out the potential to be used after Taxotere stops working. Currently, we have only one approved chemotherapy drug to treat advanced prostate cancer, Taxotere and once we become Taxotere-refractory (Taxotere stops working) all that is available to us is palliative care. The underlying theory behind CB7630 is that distant tumors, at the cellular level, manufacture their own androgens that are able to independently feed the cancer, rendering traditional hormone blockades irrelevant. Although the results from this very small trial (phase II) are positive, they are not proving to provide the great bang many had anticipated. However, my original take home message remains the same as it was in June, we need to develop new, supplementary treatment strategies that target the distant tumors at their cellular level. Joel T Nowak, MA, MSW
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