Jun 02, 2014
Tokai Pharmaceuticals Presents New Clinical Data for Galeterone among Patients with Advanced Prostate Cancer at ASCO 2014
Tokai Pharmaceuticals, Inc., a biopharmaceutical company focused on developing new treatments for prostate cancer and other hormonally driven cancers, today announced positive interim results from the Phase 2 ARMOR2 study of galeterone (TOK-001) among patients with castration-resistant prostate cancer (CRPC). These data demonstrated clinically meaningful reductions in prostate-specific androgen (PSA) levels, a marker of prostate cancer growth.
The data were presented on Saturday, May 31, in a poster presentation (abstract #5029) by Bruce Montgomery, M.D., Professor, Medical Oncology Division, University of Washington School of Medicine, and a lead investigator of the ARMOR2 trial, at the American Society of Clinical Oncology (ASCO) 2014 Annual Meeting in Chicago.
“These data expand upon those presented at the ASCO GU symposium earlier this year and continue to show robust PSA responses,” said Dr. Montgomery. “This is especially important as most patients with advanced prostate cancer develop CRPC within 12-18 months of receiving androgen-deprivation therapy, and there remains a need for new treatment options that delay the development of resistance to therapy and improve overall survival.”
The ongoing ARMOR2 trial is a two-part Phase 2 study designed to confirm the dose of galeterone (Part 1) and demonstrate safety and efficacy in distinct CRPC patient cohorts (Part 2). Part 2 is also screening for AR mutations and splice variants, including AR-V7, based on preclinical data showing galeterone activity in this setting. Approximately 132 patients are expected to be enrolled in Part 2 of the trial. At the conclusion of Part 1 of the study, a once-daily galeterone dose of 2550 mg was selected for Part 2 based upon review of safety, efficacy and pharmacokinetic data.
Interim results include data on 87 patients in Part 1 and Part 2 of the trial who were treated with galeterone at a daily dose of 2550 mg. Among 51 treatment-naïve CRPC patients, 82 percent achieved a maximal reduction in PSA levels of at least 30 percent (PSA30) and 75 percent achieved a maximal reduction in PSA levels of at least 50 percent (PSA50). Among treatment-naïve patients with metastatic CRPC, interim data in 39 patients show that 85 percent achieved a PSA30 and 77 percent achieved a PSA50. Among 15 abiraterone-refractory patients, 27 percent had a PSA decline.
In addition, a retrospective subset analysis of changes in circulating tumor cell (CTC) characteristics in treatment-naive CRPC patients identified four patients with androgen receptor truncations consistent with an androgen receptor splice variant or mutation. Androgen receptor splice variants and mutations can be associated with resistance to approved therapies for CRPC. All four patients achieved a PSA50 or greater.
Galeterone was well tolerated in all patients. The majority of adverse events were Grades 1 and 2 and the most common adverse events were nausea, diarrhea, decreased appetite, fatigue, increased aminotransferase and pruritus.
“We are encouraged by the continuing efficacy demonstrated in the data presented at ASCO,” said Jodie Morrison, president and chief executive officer of Tokai Pharmaceuticals. “These data show significant PSA responses in treatment-naïve patients, potential among abiraterone-refractory patients, and a strong safety profile. We look forward to continued data from ARMOR2 throughout 2014 including data on the utility of galeterone in patients with AR mutations and splice variants – an area of rising interest in the field.”
Galeterone, is a multi-targeted, oral small molecule drug being developed for the treatment of castration-resistant prostate cancer (CRPC) that acts by actively disrupting androgen receptor (AR) signaling, the key driver of CRPC, via multiple mechanisms of action. Galeterone combines the mechanisms of action of CYP17 inhibition and androgen receptor antagonism with an additional mechanism of androgen receptor degradation. Current available therapies disrupt the pathway at a single point. To our knowledge, galeterone is the only drug candidate in clinical trials that disrupts the pathway at multiple points. Galeterone does not bind to GABAa, eliminating the class effect risk of seizures associated with GABAa, and exhibits a selective CYP17 lyase over hydroxylase inhibition profile that does not lead to mineralocorticoid excess, and therefore, does not require concomitant dosing with prednisone.
About Tokai Pharmaceuticals
Tokai Pharmaceuticals is a biopharmaceutical company focused on developing new treatments for prostate cancer and other hormonally driven cancers. The company’s lead drug candidate, galeterone, is a highly selective multi-targeted, oral small molecule drug being developed for the treatment of patients with castration-resistant prostate cancer. Based in Cambridge, Massachusetts, Tokai is backed by Apple Tree Partners, Novartis Venture Fund and the Satter Foundation. For more information on the company and galeterone, please visit www.tokaipharma.com.