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Abiraterone Acetate (CB7630)
Abiraterone acetate (CB7630) is an orally administered inhibitor of the steroidal enzyme CYP17 (17α-hydroxylase/C17,20 lyase), a cytochrome p450 complex that is involved in testosterone production and estrogen production (see Figure below).
Scientists believe that testosterone levels in the testes and adrenals stimulate the growth of prostate cancer cells. In preclinical and clinical studies, CB7630 has demonstrated the ability to selectively inhibit the target enzyme, resulting in inhibition of testosterone production in both the adrenals and the testes.
The growth of many breast cancer cells has been shown to be estrogen dependent. Since the steroidal hormones upstream of aromatase and downstream of CYP17 could be important in the activation of estrogen and other nuclear steroid hormone receptors in breast cancer, CB7630 may impact breast cancer cell proliferation and survival by virtue of its estrogen suppressing activity.
Potential applications of CB7630 include (1) serving as second-line therapy for patients with castration-resistant prostate cancer (CRPC) who have failed treatment with docetaxel-based chemotherapy; (2) serving as second-line hormonal therapy for patients with CRPC who have failed first-line hormone therapy; and (3) serving as second-line hormonal therapy for breast cancer patients who have advanced disease despite prior hormonal therapies.
CB7630 is currently being tested in Phase I, Phase II and Phase III trials in castration-resistant prostate cancer patients at numerous locations in North America, Europe, and Australia. Based on interim clinical trial results to date, patients have experienced confirmed declines in prostate specific antigen (PSA) levels of up to 90+%, partial radiological responses (as measured by the RECIST criteria), regressing bone disease, improvement in pain and reduced opioid use. The compound has been well tolerated with minimal toxicity and no dose limiting toxicity has been observed.
A Phase I/II clinical trial of CB7630 in advanced breast cancer patients is currently underway at The Institute of Cancer Research in London and managed by the Drug Development Office of Cancer Research UK, which is funding the trial.
Further information on Cougar's clinical trials is available at http://www.clinicaltrials.gov/ct2/results?term=abiraterone.
For Abiraterone Acetate EAP, click here for information: http://www.prostatecancerearlyaccess.com
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