Galeterone

Galeterone is a steroidal compound with three claimed activities against the androgen axis at once: inhibition of CYP17 lyase, direct androgen receptor antagonism, and degradation of androgen receptor protein including the constitutively active splice variant AR-V7, which lacks the ligand-binding domain and so cannot be blocked by abiraterone or enzalutamide.

That last property was the whole commercial thesis. AR-V7 detected in circulating tumour cells predicts a poor response to abiraterone and enzalutamide, so a drug that degrades the receptor rather than blocking its ligand pocket should work where they do not. Tokai Pharmaceuticals tested the thesis in ARMOR3-SV, the only phase 3 trial in prostate cancer to select men by AR-V7 status.

The trial prescreened 953 men to find 73 who were AR-V7 positive, a prevalence of 8 percent (95 percent confidence interval 6 to 10). Of those, 38 were randomised before the data monitoring committee recommended early closure: too many men progressed and left the trial before the required radiographs. Tokai stopped developing galeterone. No approval was ever sought.