Takeda Pharmaceutical said today it ended development of orteronel (TAK-700), following disappointing results from two Phase III trials that showed the prostate cancer drug candidate missed their primary endpoints of overall survival (OS).
The studies found that in patients with metastatic, castration resistant prostate cancer (mCRPC), orteronel plus prednisone could extend the time patients lived before their cancer progressed, but did not extend OS in these patients.
“After careful consideration of the data from these trials, the company has determined that the drug has not demonstrated a clinical profile sufficient to move forward in mCRPC, given the availability of other therapies,” Takeda said in a statement, adding: “Takeda remains committed to oncology and to the treatment of prostate cancer.”
The company said it was working with trial investigators and regulatory authorities to ensure that patients who participated in the trials are transitioned to other, “appropriate” therapies.
Orteronel is an oral, nonsteroidal, selective inhibitor of 17,20-lyase, a key enzyme in the production of steroidal hormones.
On May 14, Takeda announced results from its Evaluation of the Lyase inhibitor orteronel in Metastatic Prostate Cancer 4 (ELM-PC4) trial in men with mCRPC who had not received chemotherapy. Results of ELM-PC4 showed that orteronel plus prednisone improved radiographic progression free survival (rPFS) compared to prednisone alone—one of the study’s two primary endpoints—but did not show a statistically significant improvement in the study’s second primary endpoint of OS. The median OS of patients treated with orteronel plus prednisone was 31.4 months, compared with 29.5 months for prednisone alone.
Earlier, Takeda reported results from its ELM-PC5 trial, assessing orteronel in men with mCRPC that had progressed during or following chemotherapy. That trial was unblinded in 2013 after a prespecified interim analysis indicated that orteronel plus prednisone would likely not meet the primary endpoint of improved OS when compared to the control arm. The interim analysis also showed an advantage for orteronel plus prednisone for the secondary endpoint, rPFS over the control arm.
Takeda said neither study found significant safety concerns related to orteronel.