Dench. Let's get some facts straight. This reminds me of the CB-03-01 discussion when I argued almost as the only one that the dosage was too low because I had a look at the pharmacokinetics and had knowledge of other anti-androgens. People were all so convinced it was a "vehicle" problem which was nonsense obviously. It came as no surprise that COSMO started a trial of CB-03-01 with a 2x 50MG dosage (100mg) a day.
Now on to Setipriprant;
As you can see these are all the trials where Setipiprant was in and proved to be a failure in all basically. Actelion wanted to get rid of the compound, sold it for pocket change and is proceeding with other compounds now. The initial buyover was probably extremely low. The 27 million is only for potential development and regulatory milestones.
You are correct the safety profile does look good of Setipiprant. I did throw in the 1000mg prediction based on the pharmacokinetics of Setipiprant. I can tell you that it's not going to be less than 500mg. Even at 500mg is it a viable solution with these prices? I don't think so.
I mean our goal is to sufficiently antagonize the DP2 receptor (CRTH2) right? In pure principal there is no major difference in doses for rhinitis. The goal is the same antagonize the DP2 receptor sufficiently whether that is in a cell in the hair follicle or somewhere else. What would your argumentation be for a lower dosage then let's say 500mg for example?
After all you want to use a compound that is effective. You can't rub 5mg of RU58841 or CB-03-01 and expect it to work well. Setipiprant is just a very weak compound overall with a low affinity, that's why it requires such a big dosage to "sufficiently" antagonize the DP2 receptor.
I don't exactly understand why you say that OC is "less selective". What off side targets does it have? And on what argumentation do you base that it is less safe?
The question overall and the most important one is if PGD2 blocking is really that important. Look at this point it's nothing more than a
hypothesis.
If it really works upstream after AR transcription and has a big role in the pathology of Androgenetic Alopecia then that's awesome. We could all drop our finasteride soon and hop on a DP2 antagonist like setipiprant. Obviously that's a ridiculous scenario to even consider at this point. It could be that PGD2 has a small role in Androgenetic Alopecia and blocking it won't even maintain your hair. My opinion? I think the whole PGD2 angle isn't exciting at all. I don't think blocking PGD2 will even maintain your hair. Time will tell though, I hope I am wrong though so I can drop RU and pop a DP2 antagonist in the future
.
To reiterate my point about setipiprant is that it's not really economically feasible to use enough of a dosage to antagonize the DP2 receptor at a sufficient level with these prices. So if people are interested in the PGD2 angle there are many other compounds to consider which are more potent and cheaper. That's all. If it will help anyone at a low dosage then that's great though obviously.
