At the ASCO Annual meeting in Orlando Florida, Cougar Biotechnology, Inc. announced perliminary results from their ongoing Phase II clinical trials of their much discussed investigational drug abiraterone acetate (CB7630). The company released some preliminary encouraging data in three separate poster presentations.
First, I want to tell you what abiraterone acetate is.
In scientific jargon it is an orally active acetate salt of the steroidal compound abiraterone with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis.
In plain English, it is an antiandrogen like leuprolide (Lupron, Viadur, or Eligard), goserelin (Zoladex), triptorelin (Trelstar Depot), and abarelix (Plenaxis). However, it seems to operate using a different biological pathway so it can work even when these other drugs have stopped functioning. Administration of abiraterone acetate suppresses testosterone production by both the testes and the adrenals.
THE RESULTS AS REPORTED IN THE POSTERS
Preliminary results of a phase II multicenter study of chemotherapy-naïve castration-resistant prostate cancer (CRPC) patients not exposed to ketoconazole, treated with abiraterone acetate plus prednisone (COU-AA-002)
This Phase II clinical trial is being sponsored by the Department of Defense. In this Phase II trial, CB7630 in combination with prednisone is administered once daily to chemotherapy-naïve, ketoconazole-naïve men with castration-resistant prostate cancer (CRPC), who had progressive disease despite treatment with LHRH analogues and other hormonal therapies.
In his poster discussion presentation, Dr. Ryan, the principal investigator, presented data on the 33 evaluable men treated in the trial. After 12 weeks of treatment, 26 men (79%) experienced a decline in prostate specific antigen (PSA) levels of greater than 30%, 24 (73%) experienced a PSA decline of greater than 50% and 10 (30%) experienced PSA declines of greater than 90%. For the 33 evaluable men, the median time to PSA progression was 337 days (48 weeks).
Of the 33 evaluable men, treatment with CB7630 plus prednisone resulted in radiologic disease control in 28 men (85%) with partial responses in 9 men (27%) and stable disease in 19 men (58%).
This multi-center phase II study of abiraterone acetate demonstrates anti-tumor activity in docetaxel pre-treated castration-resistant prostate cancer (CRPC) men (COU-AA-003).
This Phase II trial of CB7630 in men with advanced prostate cancer who have failed docetaxel-based chemotherapy. CB7630 is administered orally, once daily, to men with CRPC who have failed treatment with androgen deprivation therapy and failed treatment with first-line docetaxel-based chemotherapy.
The data included 47 men enrolled in this Phase II trial. CB7630 was well tolerated with only minimal toxicity in this post-docetaxel population. After 12 weeks of treatment, of the 47 men treated, 24 men (51%) experienced a decline in PSA of greater than 30%, with 19 men (40%) demonstrating a decline in PSA levels of greater than 50%, and 6 men (13%) demonstrating a decline in PSA levels of greater than 90%. Of the 47 evaluable men with measurable tumor lesions, radiologic disease control was observed in 31 of the 47 patients (66%) with 6 men (13%) experiencing confirmed partial radiological responses and 25 men (53%) experiencing stable disease. The median time to PSA progression for the 47 men in the trial was estimated to be 169 days (24 weeks).
Phase II multicenter study of abiraterone acetate plus prednisone therapy in docetaxel treated castration-resistant prostate cancer (CRPC) patients: impact of prior ketoconazole (COU-AA-004)
This poster presented data from the ongoing Phase II trial of CB7630 in combination with prednisone in patients with advanced prostate cancer who have failed androgen deprivation and docetaxel-based chemotherapy (COU-AA-004).
CB7630 in combination with prednisone is administered orally, once daily, to men with CRPC who have failed treatment with androgen deprivation therapy and have failed treatment with first-line docetaxel-based chemotherapy. To date, a total of 58 men have been enrolled in the trial at 8 different centers.
Of the 58 men, 13 men (22%) had visceral disease, 26 men (45%) had bone and soft tissue metastases, 11 men (19%) had bone metastases only and 8 men (14%) had soft tissue metastases only. Additionally, 27 men (47%) had been previously treated with ketoconazole, a drug that is currently used off-label as a secondary hormonal therapy.
The combination of CB7630 plus prednisone was well tolerated with only minimal toxicity in this post-docetaxel population. After 12 weeks of treatment, 20 men (34%) experienced a confirmed decline in PSA levels of greater than 50%. Of the 31 men who had not received prior treatment with ketoconazole, 13 men (42%) experienced a confirmed decline in PSA levels of greater than 50%. Furthermore, of the 27 men who had been previously treated with ketoconazole, 7 men (26%) experienced a confirmed decline in PSA levels of greater than 50%.
Of the 18 evaluable men with measurable tumor lesions, 3 men (17%) experienced confirmed partial radiological responses (as measured by the RECIST criteria) and 11 men (61%) experienced ongoing stable disease. For the 31 men who had not received prior treatment with ketoconazole, the median time to PSA progression was estimated to be 198 days (28 weeks). Furthermore, for the 27 men who had been previously treated with ketoconazole, the median time to PSA progression was estimated to be 99 days (14 weeks).
Source – Cougar Biotechnology, Inc.
Abiraterone acetate seems to demonstrate the ability to control tumor growth in men with chemotherapy-naïve disease as well as in men with chemotherapy-refractory disease. However, these studies are only phase II studies using a very small population and without any controls. The phase II results, so far, indicate that abiraterone acetate might hold promise for the treatment of advanced prostate cancer. Hopefully, Cougar will be able to launch the required phase III studies in an expeditious manner.
Now we wait!
Joel T Nowak MA, MSW
This is the news we hoped for. This is a better response than any other treatment in years. The median reported means that for those men who responded by psa in group 1 (79%), that most went more than a year with lowered psa. This is powerful stuff. And with a safety profile like aspirin
Also Abi reduces the production of testosterone and androgens, intracrine and autocrine. It does not act as an anti-androgen like casodex, flutamide and nilutimide.
Is this in competition with NX-1207 which is an anti-androgenic injected directly into the prostate. NX-1207 is a biologic from NYMOX Biotech in phase III.