CAMBRIDGE, Mass.--(Tokai Pharmaceuticals, Inc., a biopharmaceutical company focused on developing new treatments for prostate cancer, today announced that clinical data from the ARMOR1 Phase 1 study and preclinical data on the unique triple mechanism of action of galeterone (TOK-001) in patients with castration-resistant prostate cancer (CRPC), will be presented today by Adrian M. Senderowicz, M.D., chief medical officer and vice president, medical development, in an oral presentation titled, “Galeterone: a triple action drug for the treatment of castration-resistant prostate cancer: ARMOR1 results,” at the 2013 International Congress on Targeted Anticancer Therapies (TAT) in Paris.)--
“Our recent insights into the unique CYP17 lyase inhibition profile of galeterone have broadened our understanding of its novel triple mechanism of action and the related clinical observations in our ARMOR1 Phase 1 study”
CRPC is an advanced, difficult-to-treat form of prostate cancer that occurs when the disease progresses despite the use of androgen deprivation therapy. In preclinical studies, galeterone has demonstrated a novel triple mechanism of action to disrupt the growth and survival of prostate cancer cells by acting as a highly potent and selective CYP17 lyase inhibitor, a potent androgen receptor (AR) antagonist, and by decreasing AR levels in prostate tumors.
As recently presented at the 2013 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), when compared to the CYP17 inhibitors abiraterone acetate, ketoconazole and orteronel in preclinical studies, galeterone demonstrated potent inhibition of testosterone synthesis via selective inhibition of CYP17 lyase, and caused minimal changes in cortisol and other intermediate corticosteroids, suggesting that pharmacological levels will not cause secondary mineralocorticoid excess (ME). ME is a clinical syndrome including edema, hypokalemia and hypertension that is commonly associated with other CYP17 inhibitors and requires concomitant administration of the corticosteroid, prednisone. These preclinical data are consistent with the ARMOR1 Phase 1 clinical experience where no ME was observed, and no prednisone was required in CRPC patients.
“Our recent insights into the unique CYP17 lyase inhibition profile of galeterone have broadened our understanding of its novel triple mechanism of action and the related clinical observations in our ARMOR1 Phase 1 study,” said Martin D. Williams, president and chief executive officer, Tokai Pharmaceuticals. “Based on the encouraging Phase 1 results, we are currently evaluating a new, improved tablet formulation of galeterone with enhanced bioavailability in our ongoing ARMOR2 Phase 2 study in patients with CRPC. We look forward to learning more about the clinical utility of galeterone as a potentially differentiated treatment option for CRPC patients.”
The Phase 1 proof-of-concept clinical trial, ARMOR1, part of the ARMOR (Androgen Receptor Modulation Optimized for Response) clinical development program for the evaluation of galeterone, enrolled 49 patients and was a dose-finding study to evaluate escalating dose levels of galeterone. The study evaluated safety, reduction in prostate-specific antigen (PSA) levels and radiological response. Study results showed anti-tumor activity demonstrated by PSA reductions and soft tissue tumor shrinkage, and that galeterone was well tolerated in patients with CRPC. The maximum-tolerated dose was not reached and there were no dose-limiting toxicities or signs of secondary ME observed, and prednisone was not required.
About Galeterone (TOK-001)
Galeterone is a proprietary small molecule, oral drug for the treatment of prostate cancer that disrupts androgen receptor signaling via a novel triple mechanism of action. In preclinical studies, galeterone acted as a highly selective CYP17 lyase inhibitor, as a potent androgen receptor antagonist, and decreased androgen receptor levels in prostate tumors – the only drug in development that has been shown to exhibit all three of these properties. Galeterone combines these three distinct mechanisms of action in one therapeutic compound. Results from the ARMOR1 Phase 1 clinical trial showed that galeterone demonstrated clinical activity and was well tolerated in patients with castration-resistant prostate cancer (CRPC). Galeterone is currently being evaluated in a Phase 2 study, ARMOR2, in patients with CRPC as part of the ARMOR (Androgen Receptor Modulation Optimized for Response) clinical development program.
About Tokai Pharmaceuticals
Tokai Pharmaceuticals is a U.S. biopharmaceutical company focused on developing new treatments for prostate cancer. The company’s lead drug candidate, galeterone (TOK- 001), is the first investigational new drug that can decrease overall androgen receptor levels in prostate tumors and in which three distinct mechanisms of action are combined to disrupt androgen receptor signaling in one oncotherapeutic. Galeterone is currently being evaluated in a Phase 2 study, ARMOR2, in patients with castration-resistant prostate cancer (CRPC). Based in Cambridge, Massachusetts, Tokai is backed by Apple Tree Partners and Novartis Venture Fund. For more information on the company and galeterone, please visit www.tokaipharma.com.