About AR-V7

The growth and survival of prostate cancer tumors rely primarily on the functioning of the androgen receptor signaling pathway. This pathway is activated by the binding of male hormones, or androgens, such as testosterone and DHT, to androgen receptors in prostate cancer cells.

All proteins, including androgen receptors, are made up of a chain of amino acids that have an N-terminus at one end of the chain and a C-terminus at the other end. The C-terminal end of the androgen receptor is the region of the protein responsible for androgen binding. Tumor cells that lack the C-terminal have been shown to be unresponsive to drugs whose activity requires the binding region to remain intact, such as those that inhibit the CYP17 enzyme (like Zytiga®) or antagonize the androgen receptor (like Xtandi®).

The AR-V7 splice variant is the most common form of C-terminal loss. Based on data generated in a clinical trial conducted at Johns Hopkins University, we currently estimate that approximately 12-14% of metastatic CRPC patients who have not been treated with Zytiga or Xtandi express the AR-V7 splice variant. This percentage is believed to increase after patients are treated with either or both of Zytiga and Xtandi.

In a retrospective analysis of the seven patients enrolled in ARMOR2, our phase 2 clinical trial of galeterone, who were identified as having C-terminal loss of their androgen receptor, six of those patients (83%) showed clinically meaningful PSA reductions of at least 50%. The seventh patient discontinued therapy due to an adverse event unrelated to treatment. By contrast, in independent studies conducted at several leading academic medical centers, the presence of a truncated androgen receptor was associated with poor clinical response with Zytiga and Xtandi, with no patients achieving a PSA reduction of 50%.

We believe that AR-V7 positive patients can be reliably identified with an assay, and we have entered into a collaboration with Qiagen to develop a clinical trial assay to select patients for inclusion in our ARMOR3-SV clinical trial as well as to commercialize a companion diagnostic test for use with galeterone.


Efstathiou E et al, Eur. Urology, 2014; Antonarakis E et al, AACR, ASCO, ESMO, NEJM, 2014; Efstathiou E et al, ASCO, 2014; Scher H et al, ESMO, 2014; Nelson P, NEJM, 2014