Tokai Pharmaceuticals (Tokai) dropped a bombshell Tuesday when it announced it will discontinue its flagship ARMOR3-SV clinical trial, a pivotal Phase 3 study comparing the efficacy of Tokai’s prostate cancer drug galeterone to Astella Pharma’s product Xtandi (enzalutamide).
Tokai said in a press release that the decision to terminate the trial was made after the trial’s independent Data Monitoring Committee (DMC) determined the ARMOR3-SV trial would likely not meet its primary endpoint of demonstrating an improvement in patient survival with galeterone compared to Xtandi in this type of cancer, which has an aggressive disease course and represents a significant unmet medical need.
The drugs are designed to treat metastatic prostate cancer in patients whose prostate tumor cells express the AR-V7 splice variant, a truncated form of the androgen receptor that has been associated with non-responsiveness to commonly-used oral therapies for treatment-naïve metastatic castration-resistant prostate cancer (mCRPC), and who no longer respond to testosterone-lowering medical or surgical treatment.
Galeterone is described as an orally administered small molecule that piggybacks onto the mechanistic pathways of current second-generation hormonal prostate cancer therapies, including Zytiga (abiraterone) and Xtandi (enzalutamide), while introducing a unique third mechanism — androgen receptor degradation — that impairs the function of androgen receptors like AR-V7 by decreasing their sensitivity to androgen activity and reducing tumor growth.
The company, whose research focus is on developing and commercializing innovative therapies for prostate cancer and other hormonally driven diseases, said that in making its recommendation, the DMC cited no safety concerns associated with galeterone in the trial, and that ARMOR3-SV is the first pivotal clinical trial in treatment-naïve mCRPC to select AR-V7 positive patients.
Tokai says it plans to present data from the trial in a scientific forum once it is fully available and has been analyzed.
In January, Tokai said it expected to complete enrollment in the ARMOR3-SV trial in the second half of 2016, with the number of clinical sites projected to exceed 100 by April, and to have top-line data available by mid-2017. It had also announced plans to expand galeterone development into broader mCRPC populations, including two new studies in 2016 in patients who have shown resistance following treatment with either Zytiga or Xtandi. Galeterone had been granted Fast Track designation by U.S. FDA for treatment of mCRPC.
“We are very disappointed by this outcome. An immediate priority is to analyze the unblinded study data in detail as we evaluate potential paths forward for galeterone and our pipeline,” said Tokai President and CEO Jodie Morrison in the release. “We are deeply grateful for the support and commitment from the patients participating in the study, their caregivers, and the study investigators and their staff.”
Investors were also disappointed, with Tokai’s stock price plummeting 76 percent following the announcement to $1.23, an all-time low, as of 11:30 a.m. Tuesday, July 26, and falling further to around $1.10 by Wednesday morning.
Going forward, Tokai says it intends to evaluate its ongoing ARMOR2 Phase 2 clinical trial of galeteron in mCRPC patients with acquired resistance to Xtandi, and a planned study in patients who rapidly progress on either Xtandi or Zytiga.
Tokai has announced that it intends to allow all patients currently enrolled in the ARMOR2 and ARMOR3-SV trials to continue with the therapy following consultation with their physicians and study investigators.
An archived recording of Tokai’s July 26 update conference call is available in the Investors and Media Calendar of Events section of the Tokai website at http://www.tokaipharmaceuticals.com. The webcast will be available for replay for two weeks.