At the recent ASCO GU 2022 conference the results of the CYPIDES trial were presented. This trial tested the new drug ODM-208 which can be effective after Zytiga, Xtandi and Chemo have failed. Here are the details of this study, which is currently recruting: clinicaltrials.gov/ct2/show...
And here is a video with Dr. Fizazi presenting the results:
ncbi.nlm.nih.gov/labs/pmc/a...
"Inhibition and stimulation of activity of purified recombinant CYP11A1 by therapeutic agents" (2014)
"We found that under the experimental conditions used and when phospholipids are included, ketoconazole, posaconazole, carbenoxolone, and selegiline inhibit CYP11A1-mediated production of pregnenolone by at least 67%. Conversely, pemirolast, clobenpropit, desogestrel, dexmedetomidine, and tizanidine stimulate the enzyme activity by up to 70%."
The chemistry/science is way over my head on this one. However ODM-208 sounds like something we should pay attention to.
ODM-208 did not come out of the blue. This is an in vitro study that probably paved the way to ODM-208 among others.
So from the video I interpreted that the biomarker for those whom this will be beneficial can be identified ?
He mentions androgen receptor mutations as the biomarker. My understanding is that this is the main reason patients get resistant. However, I am not aware that a commercial test for that is available. I would just join this trial if I would qualify and not worry about these mutations. You have run out of options then anyway - apart from Lu177.
Thank you...... Great Presentation......
Good Luck, Good Health and Good Humor.
j-o-h-n Friday 03/11/2022 5:49 PM EST
As I just got another like for this post, here is a report from the presentation of ODM-208 at the ESMO 2022: urotoday.com/conference-hig... This drug is really promising.
I keep turning this over in my head. This drug is like an über abiraterone, stopping hormone/steriod synthesis at the top of the food chain rather than one step down like abiraterone does. So will that make a fundamental difference? I'm just a bit skeptical.
Apparently yes. We will have to wait for the Phase III trial and the FDA approval based on that.
Looks like you are probably right. I went down a rathole and discovered PCa can escape abiraterone treatment by mutating the AR with the T878A mutation (which I happen to have). This mutated AR then feeds on progesterone, which ODM-208 would have suppressed. Bingo!
extremely interesting, thanks for the update
Rather ironic that I noticed and made a comment to your post here a year ago.
I am going to start the process of getting approval to be in the trial for ODM-208 phase 2 ( Orion CYPIDES Trial ) asap. I will start a new post when I know I am approved to join the trial.
Yes circumstances such as having run thru Zytiga, Xtandi, and a failed 2nd attempt at Docetaxel put me in this position.
LU-177 isn't available and Jevtana isn't a good option as this 2nd attempt at Docetaxel recently beat me up pretty bad compared to Docetaxel 3 years ago.
I'm glad my MO offered/suggested this trial. I have high hopes.
Enzalutamide (Xtandi) vs Abiraterone (Zytiga) for mHSPCA
What comes after Zytiga and Xtandi have failed?
Zytiga after Xtandi? 
after xtandi and zytiga fail- 
Xtandi and Zytiga protocols
