Prostate cancer drugabiraterone and its analog galeterone are Δ5,3β-hydroxy steroids. Structures of these two agents are identical to endogenous steroid substrates (cholesterole, dehydroepiandorosterone and pregnenolone) for the 3β-hydroxysteroid dehydrogenase (3βHSD) of endocrine system. It has been reported that both of these agents are metabolized to 3-oxo-Δ4-steroids by 3βHSD in short period on oral administration. First metabolite 3-oxo-Δ4-abiraterone has more potent anti-prostate cancer properties than abiraterone where galeterone metabolite (3-oxo-Δ4-galaterone) has activity comparable to parent. Further these two metabolites undergo metabolism by 5α-reductase (5α-SRD) of endocrine system which leads to five more biologically inactive metabolites.[6] It is known that galeterone has poor oral bioavailability in rodents. Poor pharmacokinetic properties (oral absorption and metabolic half-life) of galeterone may be the reason for its clinical compromise.
Galeterone was being compared toenzalutamide in aphase IIIclinical trial (ARMOR3-SV) forAR-V7-expressing metastaticcastration-resistant prostate cancer.[8][9] Tokai announced the discontinuation of ARMOR3-SV on July 26, 2016, after a data monitoring committee determined that the trial was unlikely to meet its endpoint.[10] On August 22, 2016, the company announced the discontinuation of their phase II expansion (ARMOR2) as well.[11]
In August 2017, Tokai Pharmaceuticals discontinued the development of galeterone.[1] On December 17, 2018, it was announced that Educational & Scientific, LLC (ESL), in conjunction withUniversity of Maryland ventures, would develop the drug.[12][13][14]
^Clinical trial numberNCT02438007 for "A Study of Galeterone Compared to Enzalutamide In Men Expressing Androgen Receptor Splice Variant-7 mRNA (AR-V7) Metastatic CRPC" atClinicalTrials.gov
